Identification of a Potential Entry-Fusion Complex Based on Sequence Homology of African Swine Fever and Vaccinia Virus.

African swine fever virus (ASFV) belongs to the family of Asfarviridae, part of the group of nucleocytoplasmic large DNA viruses (NCLDV). Little is known about the internalization of ASFV in the host cell and the fusion membrane events that take place at early stages of the infection. Poxviruses, also members of the NCLDV and represented by vaccinia virus (VACV), are large, enveloped, double-stranded DNA viruses. Poxviruses were considered unique in having an elaborate entry-fusion complex (EFC) composed of 11 highly conserved proteins integrated into the membrane of mature virions. Recent advances in methodological techniques have again revealed several connections between VACV EFC proteins. In this study, we explored the possibility of an analogous ASFV EFC by identifying ten candidate proteins exhibiting structural similarities with VACV EFC proteins. This could reveal key functions of these ASFV proteins, drawing attention to shared features between the two virus families, suggesting the potential existence of an ASFV entry-fusion complex.

Impact of outpatient radiotherapy on direct non-medical cost in patients in the Central Macro Region of Peru 2021.

Background: Financial toxicity arises in cancer patients due to the objective financial burden of the disease or treatment, being associated with worse clinical outcomes. Direct non-medical spending on cancer patients undergoing radiotherapy in Peru under its publicly funded health system has not been described. Objective: To know the expenses related to the transfer of the radiotherapy outpatient. Methodology: For patients who started radiation therapy in 2021, treatment demographics and expenses related to transporting the patient from home to the radiation therapy center were prospectively collected. Association and connection tests were used, such as the Mann-Whitney/Kruskal-Wallis U-test and Spearman's Rho. A value of p < 0.05 is considered statistically significant. Results: 398 patients were collected, with average weekly expenses for transportation, lodging and food of $17.04, $6.69 and $45.91, respectively. Confirmation was positive between weekly spending and remoteness, likewise it was negative between effective teletherapy and remoteness, both analyses being statistically significant. Conclusion: The expense associated with transfer for radiotherapy is high, exceeding the average monthly income of the patient, as a consequence they have a worse therapeutic result, and may cause financial toxicity in cancer patients.

Cost analysis of three-dimensional radiation therapy versus intensity-modulated chemoradiotherapy for locally advanced cervical cancer in Peruvian citizens.

Background and objectives: The standard treatment for locally advanced cervical cancer (CC) is chemoradiotherapy (CTRT) followed by high-dose-rate brachytherapy (HDRBT). The ideal scenario would be under novel intensity-modulated radiation therapy (IMRT) volumetric-modulated arc therapy (VMAT) radiation techniques over three-dimensional (3D) radiation therapy. However, radiotherapy (RT) centres in low- and middle-income countries have limited equipment for teletherapy services like HDRBT. This is why the 3D modality is still in use. The objective of this study was to analyse costs in a comparison of 3D versus IMRT versus VMAT based on clinical staging. Materials and methods: From 02/01/2022 to 05/01/2023 a prospective registry of the costs for oncological management was carried out for patients with locally advanced CC who received CTRT ± HDRBT. This included the administration of radiation with chemotherapy. The cost associated with patient and family transfers and hours in the hospital was also identified. These expenses were used to project the direct and indirect costs of 3D versus IMRT versus VMAT. Results: The treatment regimens for stage IIIC2, including 3D and novel techniques, are those with the highest costs. The administration of 3D RT for IIIC2 and novel IMRT or VMAT techniques, is $3,881.69, $3,374.76, and $2,862.80, respectively. The indirect cost from stage IIB to IIIC1 in descending order is IMRT, 3D and VMAT, but in IIIC2 the novel technique regimens reduce by up to 33.99% compared to 3D. Conclusion: In RT centres with an available supply of RT equipment, VMAT should be preferred over IMRT/3D since it reduces costs and toxicity. However, in RT centres where demand exceeds supply in the VMAT technique planning systems, the use of 3D teletherapy over IMRT/VMAT could continue to be used in patients with stage IIB to IIIC1.

Synthesis and Biological Evaluation of C(13)/C(13')-Bis(desmethyl)disorazole†Z.

We describe the total synthesis of the macrodiolide C(13)/C(13')-bis(desmethyl)disorazole Z through double inter-/intramolecular Stille cross-coupling of a monomeric vinyl stannane/vinyl iodide precursor to form the macrocycle. The key step in the synthesis of this precursor was a stereoselective aldol reaction of a formal Evans acetate aldol product with crotonaldehyde. As demonstrated by X-ray crystallography, the binding mode of C(13)/C(13')-bis(desmethyl)disorazole Z to tubulin is virtually identical with that of the natural product disorazole Z. Likewise, C(13)/C(13')-bis(desmethyl)disorazole Z inhibits tubulin assembly with at least the same potency as disorazole Z and it appears to be a more potent cell growth inhibitor.

Is it Feasible to Use a Low-Cost Wearable Sensor for Heart Rate Monitoring within an Upper Limb Training in Spinal Cord Injured Patients?: A Pilot Study.

(1) Background: Cervical spinal cord injury (SCI) patients have impairment in the autonomic nervous system, reflected in the cardiovascular adaption level during the performance of upper limb (UL) activities carried out in the rehabilitation process. This adaption level could be measured from the heart rate (HR) by means of wearable technologies. Therefore, the objective was to analyze the feasibility of using Xiaomi Mi Band 5 wristband (XMB5) for HR monitoring in these patients during the performance of UL activities; (2) Methods: The HR measurements obtained from XMB5 were compared to those obtained by the professional medical equipment Nonin LifeSense II capnograph and pulse oximeter (NLII) in static and dynamic conditions. Then, four healthy people and four cervical SCI patients performed a UL training based on six experimental sessions; (3) Results: the correlation between the HR measurements from XMB5 and NLII devices was strong and positive in healthy people (r = 0.921 and r = 0.941 (p < 0.01) in the static and dynamic conditions, respectively). Then, XMB5 was used within the experimental sessions, and the HR oscillation range measured was significantly higher in healthy individuals than in patients; (4) Conclusions: The XMB5 seems to be feasible for measuring the HR in this biomedical application in SCI patients.

Cost analysis of total neoadjuvant therapy with 5 × 5 Gy radiation therapy versus conventional chemoradiotherapy for locally advanced rectal cancer among Peruvians.

Background and Objectives: Conventional long-course radiotherapy (LCRT) and a new paradigm of short-course radiotherapy with total neoadjuvant therapy (SCRT-TNT) are used in locally advanced rectal cancer (RC). There are few economic assessment reports available on TNT that focus on cost analysis in a country with limited funding for healthcare systems. The objective of this study was to perform a cost analysis comparing SCRT-TNT versus LCRT. Materials and Methods: In 2020-2021, a prospective registry was created to document RC patients who received neoadjuvant therapy and the costs of cancer treatments, transportation and the time patients and family members spent in the hospital. This registry outlined the direct and indirect costs of LCRT versus SCRT-TNT. Results: LCRT and SCRT-TNT regimens have direct costs that range from S/.5,993.30 to S/.27,928.36 and from S/.3,409.81 to S/.18,159.42, respectively. FOLFOX regimens are the most expensive. Administering radiotherapy in 28 3D sessions and 5 sessions of intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) sessions costs S/.2,603.88, S/.1,277.19 and S/.1,027.77, respectively. The indirect cost of FOLFOX regimens is twice that of the similar modality that combines irradiation and Oxaliplatin IV and Capecitabine VO (CAPOX). SCRT-TNT regimens with CAPOX reduce costs by at least 50%, while SCRT-TNT regimens with FOLFOX reduce costs by 32%. Conclusion: Despite using IMRT/VMAT, SCRT-TNT is a less expensive approach for patients with RC when compared to LCRT. The costs to patients using SCRT-TNT are much lower, but it is also a better option because it saves hospital resources.

Effect of Clinically Used Microtubule Targeting Drugs on Viral Infection and Transport Function.

Microtubule targeting agents (MTAs) have been exploited mainly as anti-cancer drugs because of their impact on cellular division and angiogenesis. Additionally, microtubules (MTs) are key structures for intracellular transport, which is frequently hijacked during viral infection. We have analyzed the antiviral activity of clinically used MTAs in the infection of DNA and RNA viruses, including SARS-CoV-2, to find that MT destabilizer agents show a higher impact than stabilizers in the viral infections tested, and FDA-approved anti-helminthic benzimidazoles were among the most active compounds. In order to understand the reasons for the observed antiviral activity, we studied the impact of these compounds in motor proteins-mediated intracellular transport. To do so, we used labeled peptide tools, finding that clinically available MTAs impaired the movement linked to MT motors in living cells. However, their effect on viral infection lacked a clear correlation to their effect in motor-mediated transport, denoting the complex use of the cytoskeleton by viruses. Finally, we further delved into the molecular mechanism of action of Mebendazole by combining biochemical and structural studies to obtain crystallographic high-resolution information of the Mebendazole-tubulin complex, which provided insights into the mechanisms of differential toxicity between helminths and mammalians.

[Costs of intravenous vs. subcutaneous administration of trastuzumab in peruvian patients with HER2-positive breast cancer - An observational analysis of direct and indirect costs]. / Costos de la administración intravenosa vs. subcutánea del trastuzumab en pacientes peruanas con cáncer de mama HER2 positivo. Un análisis observacional de los costos directos e indirectos.

ANTECEDENT AND OBJECTIVE: In Peru, the presentation of TZM-IV and TZM-SC is carried out. But there is no comparative cost data by route of administration. The objective of our study was to know the costs of patients with breast cancer, comparing the routes of administration in a regional cancer center in Peru. MATERIAL AND METHODS: In 2020, patients who were prescribed TZM treatment were prospectively recorded clinical, demographic and transport data, and medical costs were obtained from medical history and pharmacy records. With these data, the simulation was performed in 100 patients who received 18 cycles of the drug. RESULTS: The main contributor to the cost of the difference was the cost of the drug itself, being S/. 4,711.11 (1,323.35 USD) and S/. 4,680.30 (1,314.69 USD) for TZM-IV and TZM-SC, respectively. The administration costs to treat 100 patients with complete cycles of TZM-IV and TZM-SC were S/. 334,488.53 (93,957.45 USD) and S/.207,455.33 (58,873.97 USD), respectively. Indirect costs indicate that patients lost in total, S/. 1,123.28 (315.53 USD) and S/. 1,148.60 (322.64 USD) in TZM-IV and TZMSC per patient, respectively. CONCLUSIONS: The use of TZM-SC is recommended, in the scenario of a lower cost of the drug and a shorter duration of administration time. Especially in a country with low funding, which only allows subsidizing the direct costs of cancer treatment.

Effect of 12 Weeks Core Training on Core Muscle Performance in Rhythmic Gymnastics.

BACKGROUND: Rhythmic gymnastics performance is characterized by technical elements involving flexibility, aerobic capacity and strength. Increased core strength in rhythmic gymnastics could lead to improved sporting performance. OBJECTIVE: The aim of this study was to analyze the effect of 12 weeks of core muscle training on core muscle performance in rhythmic gymnasts. METHODS: A randomized controlled study involving 24 rhythmic gymnastics was conducted. Participants were randomly assigned to a control group (CG; n = 12; age 13.50 ± 3.17 years) or a training group (TG; n = 12; age 14.41 ± 2.35 years). Body composition, isometric strength of trunk, core endurance and core muscle electromyographic activity were measured (EMG) after 12 weeks of core training. Independent sample t-tests were carried out to compare baseline values between groups. A two-way repeated-measures analysis of variance (ANOVA) (time × group) was applied. RESULTS: The TG improved body composition, trunk lean mass (mean differences MD = -0.31; p = 0.040), lean mass (MD = 0.43; p = 0.037) and bone mass (MD = -0.06; p < 0.001) after training. Core training increased isometric strength of trunk, flexion test (MD = -21.53; p = 0.019) and extension test (MD = 22.7; p = 0.049), as well as the prone bridge core endurance test (MD = -11.27; p = 0.040). The EMG values also increased in the TG in prone bridge for front trunk (MD = -58.58; p = 0.026). CONCLUSIONS: Core strength training leads to improvements in body composition, as well as improvements in trunk strength and increases in muscle electromyographic activity. These improvements could therefore improve performance during competitive rhythmic gymnastics exercises.

CLIP-170S is a microtubule +TIP variant that confers resistance to taxanes by impairing drug-target engagement.

Taxanes are widely used cancer chemotherapeutics. However, intrinsic resistance limits their efficacy without any actionable resistance mechanism. We have discovered a microtubule (MT) plus-end-binding CLIP-170 protein variant, hereafter CLIP-170S, which we found enriched in taxane-resistant cell lines and patient samples. CLIP-170S lacks the first Cap-Gly motif, forms longer comets, and impairs taxane access to its MT luminal binding site. CLIP-170S knockdown reversed taxane resistance in cells and xenografts, whereas its re-expression led to resistance, suggesting causation. Using a computational approach in conjunction with the connectivity map, we unexpectedly discovered that Imatinib was predicted to reverse CLIP-170S-mediated taxane resistance. Indeed, Imatinib treatment selectively depleted CLIP-170S, thus completely reversing taxane resistance. Other RTK inhibitors also depleted CLIP-170S, suggesting a class effect. Herein, we identify CLIP-170S as a clinically prevalent variant that confers taxane resistance, whereas the discovery of Imatinib as a CLIP-170S inhibitor provides novel therapeutic opportunities for future trials.

Effects of whole-body vibration training on calf muscle function during maximal isometric voluntary contractions.

The purposes of this study were to determine the impact of 6 weeks of whole-body vibration training (WBVT) on maximum voluntary plantar flexor strength, muscle activity via surface electromyography (EMG), and muscle architecture measured at rest and during maximal contraction at different ankle joint angles in young healthy adults. Using a single-blind study design, 28 healthy men and women were randomly assigned to control (CG; N = 14, 7 women) or whole-body vibration training (WBVG; N = 14, 7 women) groups. Vibration training (20-25 minutes; standing with knees flexed) was performed 3 week-1 for 6 weeks (18 sessions). Maximum isometric plantar flexor torque, muscle activity (medial and lateral gastrocnemius EMG) and medial gastrocnemius fascicle angle and length at rest and maximum contraction were tested at four ankle joint angles (ranging 45° to -15°; 0° = anatomical) before and after training. Significant increases (24.7%-37.5%) were observed in peak torque (N∙m∙kg-1 ;%) at -15°, 0°, 15° and 30° joint angles from pre- to post-intervention in WBVG, which were different to CG (no change) and greater at longer muscle lengths. No between-group differences were observed in changes in EMG amplitudes measured during contraction or muscle architecture parameters at rest or during contraction. Six weeks of WBVT in young, healthy adults increased isometric plantarflexion strength at multiple joint angles, without detectible changes in EMG, muscle architecture, or body composition. Therefore, WBVT can significantly improve maximum plantar flexor strength at multiple joint angles (muscle lengths) in young healthy men, although the mechanisms underpinning the changes are currently unclear.

Synthesis of Morpholine-Based Analogues of (-)-Zampanolide and Their Biological Activity.

We describe the convergent synthesis of three prototypical examples of a new class of analogues of the complex, cytotoxic marine macrolide (-)-zampanolide that incorporate an embedded N-substituted morpholine moiety in place of the natural tetrahydropyran ring. The final construction of the macrolactone core was based on a high-yielding intramolecular HWE olefination, while the hemiaminal-linked side chain was elaborated through a stereoselective, BINAL-H-mediated addition of (Z,E)-sorbamide to a macrocyclic aldehyde precursor. The synthesis of the common functionalized morpholine building block involved two consecutive epoxide openings with tosylamide and the product of the first opening reaction, respectively, as nucleophiles. Of the three morpholino-zampanolides investigated, the N-acetyl and the N-benzoyl derivatives both exhibited nanomolar antiproliferative activity, thus being essentially equipotent with the natural product. In contrast, the activity of the N-tosyl derivative was significantly reduced.

Experiencia en el manejo de malformaciones linfáticas macroquísticas con alcohol y microquísticas con bleomicina / Experience In the Management of Macrocystic Lymphatic Malformations with Alcohol and Microcystic Malformations with Bleomycin

Las malformaciones linfáticas son anomalías raras de flujo lento y bajo que se presentan en 1 de 6.000 a 1 en 16.000 recién nacidos vivos. Las malformaciones quísticas se clasifican según su tamaño en macroquísticas, microquísticas o mixtas. Esta clasificación tiene impacto sobre el tratamiento y el pronóstico. Las malformaciones linfáticas macroquísticas tienen mejor respuesta al tratamiento, mientras que las microquísticas son difíciles de tratar y con frecuencia recidivan. El objetivo de este trabajo es describir los resultados obtenidos en pacientes con malformaciones linfáticas macro y microquísticas intervenidos con escleroterapia utilizando alcohol y bleomicina, respectivamente. Se realizó un estudio descriptivo de pacientes con malformaciones linfáticas tratadas en el Servicio de Radiología. Se incluyeron 38 pacientes, de los cuales 24 tenían lesiones macroquísticas, 10, microquísticas y 4, mixtas. El 68 % fueron tratados con alcohol y el 32 % con bleomicina. El tratamiento mostró una resolución excelente en 5 pacientes, 25 tuvieron reducción del tamaño de la lesión entre 50 y 90 %, 13 % mostró una respuesta pobre, y solo en un 7 % hubo crecimiento, a pesar del tratamiento esclerosante. De lo anterior se concluye que el tratamiento percutáneo es seguro, reduce el tamaño de las lesiones y hay pocas complicaciones informadas. Se podría utilizar como tratamiento inicial, antes de considerar una cirugía.

Lymphatic malformations are rare slow and low flow abnormalities that occur in 1 of 6,000 to 1 in 16,000 live newborns. Cystic malformations are classified according to their size as macrocystic, microcystic, or mixed. This classification has an impact on treatment and prognosis. Macrocystic lymphatic malformations have a better response to treatment, while microcystic malformations are difficult to treat and frequently recur. The objective of this study is to describe the results obtained in patients with macro and microcystic lymphatic malformations who underwent sclerotherapy using alcohol and Bleomycin, respectively. A descriptive study of patients with lymphatic malformations treated in the Radiology Service of the National Institute of Pediatrics was carried out during the period from 2014 to 2016. Thirty-eight patients were included, 24 with macrocystic, 10 microcystic and 4 mixed lesions. 68% were treated with alcohol and 32% of the patients were treated with Bleomycin. The treatment showed excellent resolution in 5 patients, 25 patients had a lesion size reduction between 50 and 90%, 13% had a poor response, and only 7% had growth despite sclerosing treatment. From the above we conclude that percutaneous treatment is safe, reduces the size of the lesions and there are few reported complications. It could be used as initial treatment before considering surgery.

A Method for the Stereoselective Construction of the Hemiaminal Center in Zampanolides.

We have developed a new method for the stereoselective establishment of the N-acyl hemiaminal moiety in zampanolide-type structures that involves the reaction of (Z,E)-sorbamide (3) with BINAL-H and subsequent amide transfer from a putative aluminum carboximidoate complex to the aldehyde moiety of a dactylolide precursor, such as 2 or 5. The method has enabled the efficient synthesis of 13-desmethylene-(-)-zampanolide (4), which was found to be an equipotent cell growth inhibitor as the natural product (-)-zampanolide (1).

N-alkylisatin-based microtubule destabilizers bind to the colchicine site on tubulin and retain efficacy in drug resistant acute lymphoblastic leukemia cell lines with less in vitro neurotoxicity.

BACKGROUND: Drug resistance and chemotherapy-induced peripheral neuropathy continue to be significant problems in the successful treatment of acute lymphoblastic leukemia (ALL). 5,7-Dibromo-N-alkylisatins, a class of potent microtubule destabilizers, are a promising alternative to traditionally used antimitotics with previous demonstrated efficacy against solid tumours in vivo and ability to overcome P-glycoprotein (P-gp) mediated drug resistance in lymphoma and sarcoma cell lines in vitro. In this study, three di-brominated N-alkylisatins were assessed for their ability to retain potency in vincristine (VCR) and 2-methoxyestradiol (2ME2) resistant ALL cell lines. For the first time, in vitro neurotoxicity was also investigated in order to establish their suitability as candidate drugs for future use in ALL treatment. METHODS: Vincristine resistant (CEM-VCR R) and 2-methoxyestradiol resistant (CEM/2ME2-28.8R) ALL cell lines were used to investigate the ability of N-alkylisatins to overcome chemoresistance. Interaction of N-alkylisatins with tubulin at the the colchicine-binding site was studied by competitive assay using the fluorescent colchicine analogue MTC. Human neuroblastoma SH-SY5Y cells differentiated into a morphological and functional dopaminergic-like neurotransmitter phenotype were used for neurotoxicity and neurofunctional assays. Two-way ANOVA followed by a Tukey's post hoc test or a two-tailed paired t test was used to determine statistical significance. RESULTS: CEM-VCR R and CEM/2ME2-28.8R cells displayed resistance indices of > 100 to VCR and 2-ME2, respectively. CEM-VCR R cells additionally displayed a multi-drug resistant phenotype with significant cross resistance to vinblastine, 2ME2, colchicine and paclitaxel consistent with P-gp overexpression. Despite differences in resistance mechanisms observed between the two cell lines, the N-alkylisatins displayed bioequivalent dose-dependent cytotoxicity to that of the parental control cell line. The N-alkylisatins proved to be significantly less neurotoxic towards differentiated SH-SY5Y cells than VCR and vinblastine, evidenced by increased neurite length and number of neurite branch points. Neuronal cells treated with 5,7-dibromo-N-(p-hydroxymethylbenzyl)isatin showed significantly higher voltage-gated sodium channel function than those treated with Vinca alkaloids, strongly supportive of continued action potential firing. CONCLUSIONS: The N-alkylisatins are able to retain cytotoxicity towards ALL cell lines with functionally distinct drug resistance mechanisms and show potential for reduced neurotoxicity. As such they pose as promising candidates for future implementation into anticancer regimes for ALL. Further in vivo studies are therefore warranted.

Structural Basis of Colchicine-Site targeting Acylhydrazones active against Multidrug-Resistant Acute Lymphoblastic Leukemia.

Tubulin is one of the best validated anti-cancer targets, but most anti-tubulin agents have unfavorable therapeutic indexes. Here, we characterized the tubulin-binding activity, the mechanism of action, and the in vivo anti-leukemia efficacy of three 3,4,5-trimethoxy-N-acylhydrazones. We show that all compounds target the colchicine-binding site of tubulin and that none is a substrate of ABC transporters. The crystal structure of the tubulin-bound N-(1'-naphthyl)-3,4,5-trimethoxybenzohydrazide (12) revealed steric hindrance on the T7 loop movement of ß-tubulin, thereby rendering tubulin assembly incompetent. Using dose escalation and short-term repeated dose studies, we further report that this compound class is well tolerated to >100 mg/kg in mice. We finally observed that intraperitoneally administered compound 12 significantly prolonged the overall survival of mice transplanted with both sensitive and multidrug-resistant acute lymphoblastic leukemia (ALL) cells. Taken together, this work describes promising colchicine-site-targeting tubulin inhibitors featuring favorable therapeutic effects against ALL and multidrug-resistant cells.

Klebsiella oxytoca enterotoxins tilimycin and tilivalline have distinct host DNA-damaging and microtubule-stabilizing activities.

Establishing causal links between bacterial metabolites and human intestinal disease is a significant challenge. This study reveals the molecular basis of antibiotic-associated hemorrhagic colitis (AAHC) caused by intestinal resident Klebsiella oxytoca Colitogenic strains produce the nonribosomal peptides tilivalline and tilimycin. Here, we verify that these enterotoxins are present in the human intestine during active colitis and determine their concentrations in a murine disease model. Although both toxins share a pyrrolobenzodiazepine structure, they have distinct molecular targets. Tilimycin acts as a genotoxin. Its interaction with DNA activates damage repair mechanisms in cultured cells and causes DNA strand breakage and an increased lesion burden in cecal enterocytes of colonized mice. In contrast, tilivalline binds tubulin and stabilizes microtubules leading to mitotic arrest. To our knowledge, this activity is unique for microbiota-derived metabolites of the human intestine. The capacity of both toxins to induce apoptosis in intestinal epithelial cells-a hallmark feature of AAHC-by independent modes of action, strengthens our proposal that these metabolites act collectively in the pathogenicity of colitis.

Recommendations for the prescription of physical exercise for patients with spondyloarthritis. / Recomendaciones para la prescripción de ejercicio físico en pacientes con espondiloartritis.

OBJECTIVE: To develop expert-based recommendations on physical activity and exercise for patients with spondyloarthritis (SpA). METHODS: Two discussion groups, one of physical therapists, rehabilitation physicians, and professionals of physical activity and sports, and another of rheumatologists interested in SpA, were held to discuss the results of a survey of rheumatologists on exercise and two focus groups with patients on barriers to exercise. Preliminary recommendations were drafted. These were submitted to the opinion of the experts in both groups according to a two round Delphi methodology. RESULTS: Twenty one recommendations covering general aspects of exercise, adaptation to patient, how to deliver messages, pain management, and type of exercise and monitoring were issued. The level of agreement varied slightly between expert groups but it was high overall. Items with poor agreement were removed from the consensus. CONCLUSIONS: We present recommendations on when and how to prescribe and monitor exercise in patients with SpA based on the opinion of experts in exercise and in SpA. We must now test whether these recommendations are useful for clinical practice and have an effect on patients with SpA seen by rheumatologists.

Scalp and skull bone metastasis in cervical carcinoma-a rare entity.

Cervical cancer is the second most common cancer in women worldwide and the first in Peru; however, metastasis to the cranial scalp is extremely rare. We present the case of a 41-year-old woman diagnosed with cervical cancer IIIB, who received treatment based on concurrent pelvic radiotherapy with chemotherapy followed by brachytherapy at the primary level with complete response, developing, at 18 months, a metastatic lesion at the scalp level without evidence of recurrence in the cervix. With the rapid growth of the metastatic lesion leading to the destruction of the cranial cap, the meninges can be observed directly, without presenting to the neurological clinic.