bluuebunny/crossref_metadata_2025 huggingface dataset:
UNUSUAL SURGERY FOR A HEPATOCARCINOMA DISGUISED AS AN ADENOMA
Authors: Perra T , Porcu A
Published: January 2023

Introduction

Hepatic neoformations should always be adequately evaluated, even if they are suspected of being benign. We present a case of suspected hepatic adenoma that turned out to be hepatocarcinoma.

Clinical case

A 38-year-old woman was admitted to the general surgery clinic due to the ultrasound finding of a hepatic neoplasm. Preoperative imaging tests and biopsy led to a diagnosis of hepatic adenoma. An abdominal CT scan showed a polylobulated expansive lesion occupying almost completely hepatic segments 5, 6 and 8 (11 cm) and an additional lesion in S8 (15 mm). The main lesion was in contact with the right hepatic vein, the middle hepatic vein, the retrohepatic vena cava, and the portal vein bifurcation. Surgical exeresis of the neoformation was performed. The surgical approach required subluxation of the liver to get direct control of the veins, rather than proceeding in an anteroposterior direction. The pathological anatomy of the mass was compatible with hepatocellular carcinoma with a solid-trabecular growth pattern and clear cell features. The heterogeneous pattern of neoplastic differentiation was indicative of a hepatocarcinoma developed on a previous adenoma.

Discussion

This case illustrates the challenges that can arise in the diagnosis of hepatocarcinoma. A correct definition and analysis of all the available elements are essential in planning the surgical treatment of liver tumors.
EFFECTIVE POROSITY OF 3D PRINTED SURGICAL MESHES
Authors: Galván Chacón V , Patrocinio Caballero D , Pagador Carrasco B , Duarte León M , Sánchez Margallo F
Published: January 2023

Introduction

According to previous studies, pore size and geometry are crucial factors to assure good clinical results for surgical meshes [refs]. Although commercial surgical meshes are commonly knitted, 3D printing has recently been used to provide additional properties to them [refs]. In general, the mechanical properties of 3D printed meshes are worse, but geometrical control is better than in knitted ones. In this study, a comparison of effective porosity between knitted and 3D printed surgical meshes was performed.

Methods

Pore size and geometry were characterized through optical brightfield microscopy (Nikon E100) and quantified using ImageJ v.1.53e. Several geometries of 3D printed meshes with polypropylene (Prusa i3 MK3 and Smartfil filament) and commercial polypropylene Assumesh meshes (Assut Europe) were evaluated. The 3D printed geometries were triangular and honeycomb while the commercial meshes were knitted.

Results

32.38, 18.65 and 17.26% of the total area of the commercial, triangular and honeycomb meshes were porous, respectively. Although effective porosity was homogeneous on commercial meshes (2.71±0.07 mm2), pore size was smaller in honeycomb (0.088±0.071 mm2) and bigger in triangular (0.201±0.063 mm2) than in commercial meshes (0.105±0.030 mm2).

Conclusions

Some imperfections are generated during the extrusion of filaments that contributes to non-uniform pores in 3D printed meshes. Hence, a post-processing of meshes will be recommended to take advantage of the higher precision of 3D printing.
ANTI-TUMORAL EFFECT OF 5-FLUOROURACIL AND OXALIPLATIN IN A LIVER REGENERATION MODEL
Authors: Novo Sukia I , Mendia Bravo M , Gil Rodríguez E , García-Alonso I , Ruiz Montesinos I , Herrero de la Parte B
Published: January 2023

Introduction

Colorectal cancer liver metastases (CRCLM) continue to be a therapeutic challenge, since their resectability is usually limited by the functionality of the liver remnant. In this context, it is necessary to study the regenerative response of the liver in a selective portal vein ligation (PVL) model, after the administration of 5-fluorouracil and oxaliplatin, and to assess the effect of compensatory hypertrophy on tumor progression.

Methods

Twenty-eight WAG/RijHsd rats carrying CRCLM were divided into four groups: control, PVL, 5FU (50mg/kg) and 5FU+Oxaliplatin (50mg/kg+10mg/kg). After 18 days of tumor development, a dose of the corresponding treatment was administered, performing a PVL of 50% 72h later. Seven days later, tumor size was quantified and a biochemical profile was performed.

Results

The 5FU+Oxaliplatin and 5FU alone treatment decreased tumor growth by 6 and 3 times compared to the PVL and control groups, respectively (p<0.001). At a biochemical level, the combination of drugs resulted in a decrease in albumin levels (3.3 ± 0.39 mg/dl; p<0.02) and a significant weight loss of 10%; however, glucose (152±6.6 mg/dl), AST (161±27.1 IU/L), and ALT (46.7±9.4 IU/L) were not significantly altered. Seven days after PVL, the liver remnant did not change in either group (5FU+Oxaliplatin: 8±1; 5FU: 9.7±1.2; control 9.4±1.9 g; p>0.05).

Conclusion

In our model, the combined therapy of 5-Fluorouracil and oxaliplatin, prior to PVL, does not affect the necessary hepatic regeneration; while the volume of tumor implants decreases, no significant alteration of the biochemical parameters is detected.
DISGUISED INGUINAL HERNIA
Authors: López J , Bosch M , Lillo C , Barreras J A , Caravaca I , García P , Arroyo A , Lacueva J
Published: January 2023

Introduction

Liposarcomas are malignant neoplasms that originate in fatty mesenchymal tissue and are the most common histological subtype of soft tissue sarcomas. They account for 1% of solid tumors in adults and are located mainly in the extremities, with the retroperitoneum being the second most frequent location. Given the rarity and aggressiveness of these tumors, it is advisable to establish a multidisciplinary approach towards them in order to improve the prognosis of patients.

Clinical case

Patient who was operated upon on a scheduled and outpatient basis for a left inguinal hernia. During surgery, a preperitoneal tumor was identified that was removed and revealed a high-grade dedifferentiated liposarcoma. In a second surgical act, a tumor mass of about 10 centimeters in length was found, lodged in the left pelvis and contacting sigma, which extended into the inguinal duct and scrotal pouch. Finally, compartment surgery and a left orchiectomy with end-to-end colo-sigmoid anastomosis were performed.

Discussion

Routine examination of the masses contained in the hernial sacs is recommended since, despite their infrequency (<0.1%), cases of liposarcomas that have their origin in the inguinal canal have been described. Surgery for retroperitoneal sarcomas must be compartmental, which requires the inclusion of viscera close to the tumor in the resection. Complete surgical resection R0 is the only potentially curative treatment. Compartment surgery should be performed by expert surgeons in referral centers with multidisciplinary teams to improve the prognosis of these patients.
NEW TECHNOLOGIES AT THE SERVICE OF THE PATIENT
Authors: Antuña Villa S , Mateos Palacios C , Soto Dopazo M , Arango Bravo A , Nuño Iglesias C , López-Mosquera Bayón E , Álvarez Iglesias B E , Fernández Fernández J C
Published: January 2023

Introduction

In the surgical field, information about operations is traditionally written down in the informed consent form, which often uses technical language that is difficult for patients to understand. Even when accompanied by verbal explanations, patients only seem to retain between 20–60% of the details.

With the purpose of improving the effectiveness of communication with our patients during the surgical process, from the Day Surgery Unit of our hospital we have developed a protocol to provide an audio-visual aid to the information supplied.

Methods

Two explanatory videos were developed for inguinal hernia repair and pilonidal cyst surgery, which were given to the patients under the care of our service using a QR code, both in the preoperative consultation and at discharge. The videos included simple explanations regarding the disease, procedure and postoperative care, in terms easily understandable to the general population. Subsequently, during postoperative follow-ups, feedback from the first 105 patients was collected.

Results

Results showed that, out of the first 105 patients who received the QR code, 72 watched the video, and of those, 100% were satisfied with the quality of the information provided and recognised that it improved their understanding of the procedure.

Conclusions

The use of new technologies, and, more specifically, of audio-visual support, could help to improve the comprehension of information received throughout surgical procedures, since it enables its repeated viewing and its sharing with relatives, which could improve the patient's overall satisfaction.
MICRO-RNA DETECTION FOR THE DIAGNOSIS OF COLON CANCER IN A MURINE MODEL
Authors: Bote J , Moreno-Lobato B , López-Nieto E , Sánchez-Margallo F M
Published: January 2023

Introduction

The main objective of this study was to characterise an animal model of colon cancer in the F344-ApcPircUwm rat through the analysis of microRNAs expressed in plasma by Next Generation Sequencing.

Methods

Colonoscopic follow-ups of the colon cancer model were performed for 10 months (n=60). At each follow-up, 2 ml of whole blood was collected in EDTA tubes, centrifuged for plasma extraction and frozen at - 80 °C. After euthanasia of the animals the different regions of the colon and their respective findings were analysed by histopathological analysis to obtain a ground truth. After this, 14 plasma samples were analysed by Next Generation Sequencing to observe the different expressions of microRNAs between the animals corresponding to the Neoplasia group and the healthy animals (n=6/8).

Results

After the corresponding functional analysis of the microRNAs deregulated in the animals of the colonic adenoma group and the healthy animals, we highlight rno-miR-192–5p, rno-miR-125b-5p and rno-miR-29c-3p, which appear underexpressed in the animals with adenomatous and adenocarcinomatous lesions in the colon.

Conclusions

The microRNAs deregulated in this animal model compared to their healthy counterpart without lesions obtained by liquid biopsy are miR-125b-5p, miR-192–5p and miR-29c-3p and their study could open the door to novel therapeutic strategies for prognosis and diagnosis by studying their expression in animal models that could be transferred to humans in the fight against colon cancer.
Socio-emotional adjustment in children attending family centres: The role of the parent–child relationship
Authors: Calatrava Maria , Swords Lorraine , Spratt Trevor
Published: January 2023

Family services offer the possibility of producing data sets, capable of primary analyses to measure service efficacy, and secondary analyses to develop nuanced understandings of family needs. In this article, we report secondary analysis of data drawn from 1,151 families elicited upon intake to family centres in Ireland. The aim was to examine correlates of children’s socio-emotional functioning, with focus on the quality of relationships between children and parents. Participating families completed surveys containing socio-demographic questions and standardised instruments tapping into children’s social, emotional and behavioural strengths and difficulties, parents’ mental health, and closeness and conflict in parent–child relationship. Findings indicated that parents’ perceptions of their children’s socio-emotional functioning significantly influenced the quality of the child–parent relationship. Higher levels of conflict were significantly associated with psychological difficulties, whilst greater closeness was significantly related to prosocial behaviours. These relationships held after controlling for a range of child, parent and family socio-demographic variables, such as the child’s experience of chronic illness or stressful life events, both of which independently predicted poorer outcomes. Results are discussed in terms of the dynamic, reciprocal nature of family relationships whereby parent–child conflict and children’s problematic socio-emotional functioning likely influence, and are influenced by, each other.
Ap4b1-knockout mouse model of hereditary spastic paraplegia type 47 displays motor dysfunction, aberrant brain morphology and ATG9A mislocalization
Authors: Scarrott Joseph M , Alves-Cruzeiro João , Marchi Paolo M , Webster Christopher P , Yang Zih-Liang , Karyka Evangelia , Marroccella Raffaele , Coldicott Ian , Thomas Hannah , Azzouz Mimoun
Published: January 2023

Mutations in any one of the four subunits (ɛ4, β4, μ4 and σ4) comprising the adaptor protein Complex 4 results in a complex form of hereditary spastic paraplegia, often termed adaptor protein Complex 4 deficiency syndrome. Deficits in adaptor protein Complex 4 complex function have been shown to disrupt intracellular trafficking, resulting in a broad phenotypic spectrum encompassing severe intellectual disability and progressive spastic paraplegia of the lower limbs in patients. Here we report the presence of neuropathological hallmarks of adaptor protein Complex 4 deficiency syndrome in a clustered regularly interspaced short palindromic repeats-mediated Ap4b1-knockout mouse model. Mice lacking the β4 subunit, and therefore lacking functional adaptor protein Complex 4, have a thin corpus callosum, enlarged lateral ventricles, motor co-ordination deficits, hyperactivity, a hindlimb clasping phenotype associated with neurodegeneration, and an abnormal gait. Analysis of autophagy-related protein 9A (a known cargo of the adaptor protein Complex 4 in these mice shows both upregulation of autophagy-related protein 9A protein levels across multiple tissues, as well as a striking mislocalization of autophagy-related protein 9A from a generalized cytoplasmic distribution to a marked accumulation in the trans-Golgi network within cells. This mislocalization is present in mature animals but is also in E15.5 embryonic cortical neurons. Histological examination of brain regions also shows an accumulation of calbindin-positive spheroid aggregates in the deep cerebellar nuclei of adaptor protein Complex 4-deficient mice, at the site of Purkinje cell axonal projections. Taken together, these findings show a definitive link between loss-of-function mutations in murine Ap4b1 and the development of symptoms consistent with adaptor protein Complex 4 deficiency disease in humans. Furthermore, this study provides strong evidence for the use of this model for further research into the aetiology of adaptor protein Complex 4 deficiency in humans, as well as its use for the development and testing of new therapeutic modalities.
Skin testing might have a diagnostic role in immune complex-mediated hypersensitivity reactions
Authors: Triwatcharikorn Jidapa , Pholmoo Natthiya , Ratanasutiranont Narumol , Rerknimitr Pawinee , Klaewsongkram Jettanong
Published: January 2023

Clinical applications of skin testing are known to help diagnose IgE-mediated and T-cell-mediated delayed cutaneous reactions. By contrast, drug-induced immune complex-mediated vasculitis is primarily diagnosed based on medical history, clinical setting and laboratory evidence of immune-complex formation, as there are no proven methods to identify the suspect culprit. We report three cases of drug- or biologic-induced immune complex-mediated vasculitis, in which the culprit agents could be confirmed by a positive intradermal test with later reading (between 12 and 24 h after the test), with verification by immunohistochemical or immunofluorescent results. The findings of our study suggest that skin tests with a delayed reading could have a potential role in diagnosing some instances of immune complex-mediated hypersensitivity reactions.
#corticophobia: a review on online misinformation related to topical steroids
Authors: Finnegan Paula , Murphy Michelle , O’Connor Cathal
Published: January 2023

Misinformation in healthcare is at crisis level worldwide, with the internet as primary source of prevarication. Topical corticosteroids (TCS) are a safe and effective treatment used in multiple dermatological conditions. Nonadherence to prescribed TCS can be due to phobia secondary to misinformation. TCS phobia is a complex multifaceted phenomenon that exploits patients with skin disease, creates cognitive dissonance and can obstruct successful treatment. This study aimed to examine the content of TCS-related misinformation available online. A formal review of PubMed was performed using the terms ‘topical corticosteroids’ AND ‘misinformation’ OR ‘disinformation’ OR ‘conspiracy theory, along with an informal Google search using combinations of these terms and further targeted searches on social media applications including Facebook™, Twitter™, Instagram™ and TikTok™. ‘Topical steroid withdrawal’, ‘red skin syndrome’ or ‘TCS addiction’ is a particularly prevalent myth currently being propagated on social media, with most content suggesting that eczema is due to a ‘leaky gut’ or food intolerance and not to skin inflammation. The risks of potential adverse effects such as skin thinning and stunted growth/development are often exaggerated. Multiple websites promoting misinformation were frequently endorsed by companies advertising consultations or testing to identify ‘underlying causes’, or ‘natural’ products as alternative treatments, including ‘herbal’ remedies, which can contain significant quantities of corticosteroids or other potent ingredients. The dermatology community should be vigilant of the type of TCS-related misinformation online and be active in attempts to counteract it with evidence-based advice.
Focal alopecia associated with a plaque
Authors: Wright William A , Kamp Erin , Musbahi Esra , Martin Blanca , Farrant Paul
Published: January 2023

We report the case of a 65-year-old woman presenting with a 15-month history of recurrent episodes of focal alopecia at the site of a bluish plaque on the vertex of her scalp. Histopathological examination revealed an admixture of focally nested oval, dendritic or epithelioid melanocytes together with slender spindle cells and occasional melanocytes. The spindle cells were positive for S100 and focally positive for epidermal membrane antigen, while the melanocytes were positive for S100 and Melan A.
Liver fibrosis for the dermatologist: a review
Authors: Raahimi Mina M , Livesey Amy , Hamilton Jessica , Shipman Alexa R , Aspinall Richard J
Published: January 2023

Methotrexate-induced liver fibrosis is not a well-defined pathology, and many of the reported cases can instead be classified as nonalcoholic fatty liver disease by current diagnostic criteria, which is particularly common in the psoriasis cohort. Liver fibrosis usually takes many years to progress; therefore, screening for liver fibrosis should be done no more regularly than annually at the very most in dermatology practice. An algorithm is presented about how to investigate abnormal liver blood tests and screening tools for liver fibrosis are compared.
Detection of FIP1L1–PDGFRA fusion gene-positive cells in the skin lesion of a patient with hypereosinophilic syndrome
Authors: Kitayama Shohei , Makino Teruhiko , Yoto Ayumi , Mori Shuichi , Furukawa Fumina , Torai Ryotaro , Mizawa Megumi , Shimizu Tadamichi
Published: January 2023

Hypereosinophilic syndrome (HES) is a heterogeneous group of diseases, characterized by persistent hypereosinophilia and end-organ damage. The FIP1L1–PDGFRA (F/P) fusion gene is found in 3–25% of patients with HES and is an oncogenic driver of myeloid neoplasms with clonal eosinophilia. Although cutaneous symptoms are the most common type of symptom in patients who have F/P fusion gene-positive HES (F/P HES), histological reports are limited. We herein present the case of a 78-year-old man with erythematous macules and severe pruritus on his trunk and extremities. Laboratory investigations revealed marked eosinophilia and elevated serum vitamin B12. A histological examination showed massive infiltration of eosinophils and mast cells around the vessels in the upper dermis. Fluorescence in situ hybridization revealed F/P fusion genes in nuclei in the peripheral blood and the skin lesion. The patient was diagnosed with F/P HES, and showed an excellent clinical and haematological response to imatinib.
Diffuse cutaneous melanosis is an under-recognized sign with a poor prognosis in patients with melanoma
Authors: Coe James , Smith Hayley , Edward Sara , Dunwoodie Elaine , Hook Jane , Marples Maria , Mitra Angana
Published: January 2023

We report the largest single-centre case series of diffuse cutaneous melanosis in the literature. This is a rare clinical presentation seen in patients with malignant melanoma that is important to recognize as it may be the first sign of distant metastases and has a very poor prognosis.
Recommendation to update the British Society for Cutaneous Allergy corticosteroid series
Authors: Morrow Sarah E , Arianayagam Sanju , Wilkinson Mark , Bourke John , Bertram Chandra Gooptu , Buckley Deirdre A , Chowdhury Mahbub M U , Divekar Preshita , Ghaffar Sharizan Abdul , Green Cathy , Holden Catherine , Johnston Graham A , Mughal Avad , Dhonncha Eilis Nic , Reckling Christine , Scharrer Krisztina , Stone Natalie , Thompson Donna , Wakelin Sarah , Cooper Susan
Published: January 2023

Background

Patch testing is an important investigation when dermatitis is unresponsive to, or worsened by, topical corticosteroid treatment. There is a balance to be struck between testing too many allergens, which is expensive, time consuming and risks causing sensitization, and testing too few, which risks missing the diagnosis. The current British Society for Cutaneous Allergy (BSCA) corticosteroid series comprises eight allergens and was last updated in February 2007.

Aim

To review and update the BSCA corticosteroid series.

Methods

We retrospectively analysed data from 16 patch test centres in the UK and Ireland for all patients who were patch tested to a corticosteroid series between August 2017 and July 2019. We recorded the allergens tested, the number and percentage tested to a corticosteroid series and the number of positive results for each allergen. We identified the allergens that test positive in ≥ 0.1% of selectively tested patients.

Results

Overall, 3531 patients were tested to a corticosteroid series in the 16 centres. The number of allergens tested ranged from 7 to 18 (mean 10). The proportion of patch test patients who were tested to a corticosteroid series ranged from 1% to 99%. Six allergens in the 2017 BSCA series tested positive in ≥ 0.1% of patients. Nine allergens not in the BSCA corticosteroid series tested positive in ≥ 0.1% of patients.

Conclusion

This audit demonstrates the importance of regular review of recommended series and the significant variations in practice. The new BSCA corticosteroid series that we recommend contains 13 haptens, with the addition of the patient’s own steroid creams as appropriate.
A case of Sézary syndrome in a patient during treatment with baricitinib for seronegative rheumatoid arthritis
Authors: Saito Kandai , Shimauchi Takatoshi , Kageyama Reiko , Furukawa Seri , Suzuki Norihito , Ginoza Atsuyoshi , Moriki Mutsumi , Ito Taisuke , Honda Tetsuya
Published: January 2023

The risk of developing malignancies including cutaneous T-cell lymphoma with use of Janus kinase inhibitors is of concern. Here, we describe a case of Sézary syndrome in a patient during treatment with baricitinib for seronegative rheumatoid arthritis.
Role of ultra-high-frequency ultrasound in the diagnosis and management of basal cell carcinoma: pilot study based on 117 cases
Authors: Chauvel-Picard Julie , Tognetti Linda , Cinotti Elisa , Habougit Cyril , Suppa Mariano , Lenoir Clement , Rubegni Pietro , Del Marmol Veronique , Berot Vincent , Gleizal Arnaud , Vercherin Paul , Dejonckheere Guillame , Raffaelli Charles , Cardot-Leccia Nathalie , Azulay Nicholas , Sudaka-Bahadoran Anne , Perrot Jean L , Bahadoran Philippe
Published: January 2023

Background

Ultrasound imaging has recently benefited from the introduction of a new 70 MHz transducer able to provide high-resolution images, i.e. ultra-high-frequency ultrasound (UHFUS).

Aim

To study the morphological features of basal cell carcinomas (BCCs) and measure BCC thickness by means of UHFUS examination.

Methods

In this retrospective multicentric study, 171 consecutive patients underwent UHFUS examination between November 2018 and May 2019 for suspected BCC. Diagnosis was confirmed by histopathology. A series of morphological parameters including echogenicity, structure, borders, shape composition (presence of intralesional structures) were investigated along with objective measurements such as thickness (maximum distance between the surface of the epidermis and the deepest part of the tumour) and width.

Results

In total, 117 BCCs from 93 patients were examined, including superficial (n = 13; 11.1%), nodular (n = 64; 54.7%), infiltrative (n = 18; 15.4%), mixed subtypes (n = 20; 17.1%) and other subtypes (n = 2; 1.7%). The most frequently observed UHFUS parameters included: hypoechoic signal (n = 80; 68.4%, P < 0.001), homogeneous structure (n = 76, 65.0%, P = 0.01), well-defined borders (n = 77, 65.8%, P < 0.001) and elongated shape (n = 71, 60.7%, P < 0.001). An excellent correlation was found between the BCC thickness measured by UHFUS and the value estimated by histology (interclass correlation ≥ 0.80).

Conclusion

UHFUS is a new rapid and easy noninvasive skin imaging technique able to provide data on the dimensions and morphology of BCCs in real time and at the bedside. These characteristics mean UHFUS has a number of possible applications, ranging from presurgical mapping to the detection of disease recurrence and treatment monitoring.
Paradoxical hidradenitis suppurativa due to anti-interleukin-1 agents for mevalonate kinase deficiency successfully treated with the addition of ustekinumab
Authors: López Sanz Pablo , Guzmán Pérez Marta , Azaña Defez José Manuel , Guerrero Ramírez Claudia , Manso Córdoba Silvia , Alfaro Martínez María Encarnación
Published: January 2023

Hidradenitis suppurativa (HS) as a paradoxical adverse event (PAE) from using anti-interleukin (IL)-1 has not been reported in the literature, to our knowledge. We herein report a case of paradoxical HS as a result of use of anti-IL-1 agents for mevalonate kinase deficiency disease that was successfully treated with the addition of ustekinumab.
Preparation of mesoporous silica nanocarriers targeting glucose-6-phosphate isomerase inhibition and application in the treatment of rheumatoid arthritis
Authors: Zong Ming , Cheng Yu , Ye Bei , Chen Saige , Yu Shanshan , Ding Menglei , Lu Liu , Fan Lieying
Published: January 2023

Glucose 6-phosphate isomerase (G6PI) is an indicator to assist in diagnosis of rheumatoid arthritis (RA) and monitor the disease. It also plays a key role in proliferating RA synovial tissues, pannus formation, and invasion and destruction of articular cartilage. In this study, we synthesized nanoparticles targeting G6PI (siG6PI-MSN) using mesoporous silica nanocarriers (MSN) and small interfering RNA (siRNA), followed by identifying the characteristics and functions, and preliminarily exploring their application in the treatment of RA in vivo with a type II collagen-induced arthritis (CIA) rat model. It showed that the synthetic functionalized carrier had a regular pore structure and a specific volume and surface area. No obvious hemolysis or toxicity of the carrier was found when its concentration was below 100 µg/ml. Cytological results in vitro suggested that siG6PI-MSN significantly inhibited G6PI expression and reduced the ability of proliferation, migration, and invasion of FLSs, compared with the siNC-MSN group. In vivo results in the CIA rat model showed that the arthritis index and degree of joint swelling among rats in the siG6PI-MSN-treatment group were significantly lower than those in the control group. Moreover, the number of FLSs in Synovium and the levels of TNF α and IL-1 β were also significantly decreased in the siG6PI-MSN group. Histopathology of the synovial tissue and cartilage revealed siG6PI-MSN treatment significantly reduced the pathological manifestations of arthritis. In conclusion, siG6PI-MSN effectively suppresses the proliferation and invasive growth of synovial tissue and improve joint swelling and inflammatory infiltration, thereby preventing joint damage in RA. This carrier may be a new therapeutic measure for RA, with potential social and economic benefits.
Not too little, not too much: the impact of mutation types in Wiskott-Aldrich syndrome and RAC2 patients
Authors: Hsu Amy P
Published: January 2023

Primary immune deficiencies (PIDs) are genetic disorders impacting the appropriate development or functioning of any portion of the immune system. The broad adoption of high-throughput sequencing has driven discovery of new genes as well as expanded phenotypes associated with known genes. Beginning with the identification of WAS mutations in patients with severe Wiskott-Aldrich Syndrome, recognition of WAS mutations in additional patients has revealed phenotypes including isolated thrombocytopenia and X-linked neutropenia. Likewise RAC2 patients present with vastly different phenotypes depending on the mutation–ranging from reticular dysgenesis or severe neutrophil dysfunction with neonatal presentation to later onset common variable immune deficiency. This review examines genotype-phenotype correlations in patients with WAS (Wiskott-Aldrich Syndrome) and RAC2 mutations, highlighting functional protein domains, how mutations alter protein interactions, and how specific mutations can affect isolated functions of the protein leading to disparate phenotypes.
Effects of working memory span training on top-down attentional asymmetry at both neural and behavioral levels
Authors: Li Yang , Chen Xiongying , Zhang Qiumei , Xu Wending , Li Jin , Ji Feng , Dong Qi , Chen Chuansheng , Li Jun
Published: January 2023

The leftward asymmetry of the visual field and posterior brain regions, a feature of the normal attention process, can be strengthened by brain stimulation, e.g. administering alpha frequency stimulation to the left posterior cortex. However, whether it can be strengthened by cognitive training, especially with nonlateralized tasks, is unknown. We used a dataset from a 2-month-long randomized controlled trial and compared the control group with 2 training groups trained with backward or forward memory span tasks. A lateralized change detection task with varied memory loads was administered as the pre-, mid-, and post-tests with simultaneous electroencephalographic recording. Intrasubject response variability (IRV) and the alpha modulation index (MI) were calculated. Analysis of IRV showed more enhanced leftward attentional bias in the backward group than in the other groups. Consistently, analysis of MI found that its enhancements in the left hemisphere (but not the right hemisphere) of the backward group were significantly higher than those of the other groups. Further analysis revealed that left MI changes predicted left IRV improvement. All of these results indicated that backward memory span training enhanced leftward attentional asymmetry at both the behavioral and neural levels.
The precuneus as a central node in declarative memory retrieval
Authors: Flanagin Virginia L , Klinkowski Svenja , Brodt Svenja , Graetsch Melanie , Roselli Carolina , Glasauer Stefan , Gais Steffen
Published: January 2023

Both, the hippocampal formation and the neocortex are contributing to declarative memory, but their functional specialization remains unclear. We investigated the differential contribution of both memory systems during free recall of word lists. In total, 21 women and 17 men studied the same list but with the help of different encoding associations. Participants associated the words either sequentially with the previous word on the list, with spatial locations on a well-known path, or with unique autobiographical events. After intensive rehearsal, subjects recalled the words during functional magnetic resonance imaging (fMRI). Common activity to all three types of encoding associations was identified in the posterior parietal cortex, in particular in the precuneus. Additionally, when associating spatial or autobiographical material, retrosplenial cortex activity was elicited during word list recall, while hippocampal activity emerged only for autobiographically associated words. These findings support a general, critical function of the precuneus in episodic memory storage and retrieval. The encoding-retrieval repetitions during learning seem to have accelerated hippocampus-independence and lead to direct neocortical integration in the sequentially associated and spatially associated word list tasks. During recall of words associated with autobiographical memories, the hippocampus might add spatiotemporal information supporting detailed scenic and contextual memories.
The waiting game: investigating the neurobiological transition from acute to persistent pain in adolescent rats
Authors: Salberg Sabrina , Doshen Angela , Yamakawa Glenn R , Miller Jillian Vinall , Noel Melanie , Henderson Luke , Mychasiuk Richelle
Published: January 2023

Persistent postsurgical pain affects 20% of youth undergoing a surgical procedure, with females exhibiting increased prevalence of chronic pain compared with males. This study sought to examine the sexually-dimorphic neurobiological changes underlying the transition from acute to persistent pain following surgery in adolescence. Male and female Sprague Dawley rats were randomly allocated to a sham or injury (plantar-incision surgery) condition and assessed for pain sensitivity while also undergoing magnetic resonance imaging at both an acute and chronic timepoint within adolescence. We found that injury resulted in persistent pain in both sexes, with females displaying most significant sensitivity. Injury resulted in significant gray matter density increases in brain areas including the cerebellum, caudate putamen/insula, and amygdala and decreases in the hippocampus, hypothalamus, nucleus accumbens, and lateral septal nucleus. Gray matter density changes in the hippocampus and lateral septal nucleus were driven by male rats whereas changes in the amygdala and caudate putamen/insula were driven by female rats. Overall, our results indicate persistent behavioral and neurobiological changes following surgery in adolescence, with sexually-dimorphic and age-specific outcomes, highlighting the importance of studying both sexes and adolescents, rather than extrapolating from male adult literature.
Neurophysiological principles of inhibitory control processes during cognitive flexibility
Authors: Yu Shijing , Stock Ann-Kathrin , Münchau Alexander , Frings Christian , Beste Christian
Published: January 2023

Inhibitory control plays an indispensable role in cognitive flexibility. Nevertheless, the neurophysiological principles underlying this are incompletely understood. This owes to the fact that the representational dynamics, as coded in oscillatory neural activity of different frequency bands has not been considered until now—despite being of conceptual relevance. Moreover, it is unclear in how far distinct functional neuroanatomical regions are concomitantly involved in the processing of representational dynamics. We examine these questions using a combination of EEG methods. We show that theta-band activity plays an essential role for inhibitory control processes during cognitive flexibility across informational aspects coded in distinct fractions of the neurophysiological signal. It is shown that posterior parietal structures and the inferior parietal cortex seem to be the most important cortical region for inhibitory control processes during cognitive flexibility. Theta-band activity plays an essential role in processes of retrieving the previously inhibited representations related to the current task during cognitive flexibility. The representational content relevant for inhibitory processes during cognitive flexibility is coded in the theta frequency band. We outline how the observed neural mechanisms inform recent overarching cognitive frameworks on how flexible action control is accomplished.
A Changed Constitutional Perception of International Law: Demonstrating the Move Ahead With a Turned Back Head?
Authors: Marochkin Sergey Yu
Published: January 2023

Russia has entered a new epoch in its attitude to international law by adopting two small amendments to the Constitution. The 2020 Law “On an Amendment to the Constitution of the Russian Federation” introduced a package of numerous modifications. A few key ones deal with international law. Formally, they relate to the very particular issue on the possibility of refusing to comply with the decisions of international jurisdictional bodies, but in essence, they reflect a fundamental change in the country’s attitude to its obligations in the international community and the role of international law in general. The article assesses the significance of these amendments for the Russian legal system and shows the origins of such a change which was first indicated by the decision of the Russian Constitutional Court (RCC) and the federal constitutional law in 2015. Now this change is incorporated into the Constitution. Supporters of the changes are trying to assure that Russia follows the experience of western countries that conduct a similar policy towards the international courts. The article asserts that the argumentation used in such statements is incomplete and inexact; the real situation of relations between western countries and these courts is different. Russia is essentially the only country with an approved position on the acts of international jurisdictional bodies. It is shown that ensuring the supremacy of the Constitution by the amendments is senseless from a legal point of view. The true meaning of them is to erect barriers to “inconvenient” decisions of international bodies. Failure to comply with them entails a violation of obligations under international law. The amendments are to illustrate a demonstrative movement forward, presumably in line with current realities but in fact, this is a movement with a head turned back, a returning to the past. This policy has already become one of logical steps to Russia’s withdrawal from the Council of Europe (CoE).
Yield of Facility-based Targeted Universal Testing for Tuberculosis With Xpert and Mycobacterial Culture in High-Risk Groups Attending Primary Care Facilities in South Africa
Authors: Berhanu Rebecca H , Lebina Limakatso , Nonyane Bareng A S , Milovanovic Minja , Kinghorn Anthony , Connell Lucy , Nyathi Sipho , Young Katherine , Hausler Harry , Naidoo Pren , Brey Zameer , Shearer Kate , Genade Leisha , Martinson Neil A
Published: January 2023

Background

We report the yield of targeted universal tuberculosis (TB) testing of clinic attendees in high-risk groups.

Methods

Clinic attendees in primary healthcare facilities in South Africa with one of the following risk factors underwent sputum testing for TB: human immunodeficiency virus (HIV), contact with a TB patient in the past year, and having had TB in the past 2 years. A single sample was collected for Xpert-Ultra (Xpert) and culture. We report the proportion positive for Mycobacterium tuberculosis. Data were analyzed descriptively. The unadjusted clinical and demographic factors’ relative risk of TB detected by culture or Xpert were calculated and concordance between Xpert and culture is described.

Results

A total of 30 513 participants had a TB test result. Median age was 39 years, and 11 553 (38%) were men. The majority (n = 21734, 71%) had HIV, 12 492 (41%) reported close contact with a TB patient, and 1573 (5%) reported prior TB. Overall, 8.3% were positive for M. tuberculosis by culture and/or Xpert compared with 6.0% with trace-positive results excluded. In asymptomatic participants, the yield was 6.7% and 10.1% in symptomatic participants (with trace-positives excluded). Only 10% of trace-positive results were culture-positive. We found that 55% of clinic attendees with a sputum result positive for M. tuberculosis did not have a positive TB symptom screen.

Conclusions

A high proportion of clinic attendees with specific risk factors (HIV, close TB contact, history of TB) test positive for M. tuberculosis when universal testing is implemented.
Safety and Immunogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine given with and without AS03 or MF59 adjuvants in healthy adults
Authors: Winokur Patricia L , Hegmann Theresa E , Keitel Wendy A , Bernstein David I , Frey Sharon E , Bryant Chris ,   DMID 15-0064 Study Group, Stapleton Jack , Meier Jeffery , Ince Dilek , Patel Shital M , El Sahly Hana , Atmar Robert , Anderson Edwin , Graham Irene , Hoft Daniel
Published: January 2023

Background

Avian influenza A/H5N8 virus infections have been circulating widely in wild and domestic bird populations with transmission to a few human poultry workers. This phase 1, randomized, blinded trial evaluated the safety and immunogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine (H5N8 IIV) given with and without AS03 or MF59 adjuvants.

Methods

275 healthy adults, ages 19-64 years, were randomized to one of five groups to receive two doses of 15 µg unadjuvanted influenza A/gyrfalcon/Washington/41088-6/2014(H5N8) (clade 2.3.4.4c) virus vaccine or two doses of 7.5 or 15 µg of vaccine adjuvanted with AS03 or MF59. Immunogenicity was assessed through 21 days following the second dose of vaccine using hemagglutination inhibition (HAI) and microneutralization (MN) assays for the homologous influenza A/H5N8 and three heterologous influenza A/H5 viruses. Safety was assessed through 1 year.

Results

The vaccines were well tolerated. Only modest immune responses were seen following receipt of a single dose of vaccine. Seroprotection (HAI titers ≥40) was more common in groups that received AS03 plus 7.5 or 15 µg of vaccine (89% and 93%, respectively) compared to the MF59-adjuvanted groups (56% and 73%), while unadjuvanted vaccine showed a poor response (27%). Higher antigen content resulted in modestly improved immune responses. HAI and MN GMTs and seroconversion rates were low across all study groups for all three heterologous strains of influenza A/H5 virus.

Conclusions

AS03 or MF59-adjuvanted H5N8 IIV generated strong immunogenic responses following two doses. There was poor cross-reactivity for the three antigenically drifted H5N1 strains tested.
Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial
Authors: Malchair Pierre , Giol Jordi , García Vanesa , Rodríguez Orlando , Ruibal José Carlos , Zarauza Alvaro , Llopis Ferrán , Matellán Leire , Bernal Tania , Solís Beatriz , Otero Aurema , Carnaval Thiago , Jofre Hector , Jacob Javier , Solanich Xavier , Antolí Arnau , Rocamora Gemma , Videla Sebastián
Published: January 2023

Background

We aimed to evaluate icatibant, a competitive antagonist of the bradykinin B2 receptors, for the treatment of inpatients with coronavirus disease 2019 (COVID-19) pneumonia admitted in the early hypoxemic stage.

Methods

The randomized, open-label clinical trial of icatibant for COVID-19 pneumonia (ICAT·COVID, registered as NCT04978051 at ClinicalTrials.gov) was conducted in Barcelona. Inpatients requiring supplemental but not high-flow oxygen or mechanical ventilation were allocated (1:1) to treatment with either three 30-mg icatibant doses/d for 3 consecutive days plus standard care or standard care alone, and followed for up to 28 days after initial discharge. The primary and key secondary outcomes were clinical response on study day 10/discharge and clinical efficacy at 28 days from initial discharge, respectively.

Results

Clinical response occurred in 27 of 37 patients (73.0%) in the icatibant group and 20 of 36 patients (55.6%) in the control group (rate difference, 17.42; 95% confidence interval [CI], −4.22 to 39.06; P = .115). Clinical efficacy ensued in 37 patients (100.0%) in the icatibant group and 30 patients (83.3%) in the control group (rate difference, 16.67; 95% CI, 4.49-28.84; P = .011). No patient died in the icatibant group, compared with 6 patients (16.7%) in the control group (P = .011). All patients but 1 had adverse events, which were evenly distributed between study arms. No patient withdrew because of adverse events.

Conclusions

Adding icatibant to standard care was safe and improved both COVID-19 pneumonia and mortality in this proof-of-concept study. A larger, phase 3 trial is warranted to establish the clinical value of this treatment.

Clinical Trials Registration

NCT04978051.
War in Ukraine and dialysis treatment: human suffering and organizational challenges
Authors: Novakivskyy Volodymyr , Shurduk Roman , Grin Inna , Tkachenko Taisiia , Pavlenko Nataliia , Hrynevych Anastasiia , Hymes Jeffrey L , Maddux Franklin W , Stuard Stefano
Published: January 2023

In January 2021, there were 9648 patients in Ukraine on kidney replacement therapy, including 8717 on extracorporeal therapies and 931 on peritoneal dialysis. On 24 February 2022, foreign troops entered the territory of Ukraine. Before the war, the Fresenius Medical Care dialysis network in Ukraine operated three medical centres. These medical centres provided haemodialysis therapy to 349 end-stage kidney disease patients. In addition, Fresenius Medical Care Ukraine delivered medical supplies to almost all regions of Ukraine. Even though Fresenius Medical Care's share of end-stage kidney disease patients on dialysis is small, a brief narrative account of the managerial challenges that Fresenius Medical Care Ukraine and the clinical directors of the Fresenius Medical Care centres had to face, as well as the suffering of the dialysis population, is a useful testimony of the burden imposed by war on these frail, high-risk patients dependent on a complex technology such as dialysis. The war in Ukraine is causing immense suffering for the dialysis population of this country and has called for heroic efforts from dialysis personnel. The experience of a small dialysis network treating a minority of dialysis patients in Ukraine is described. Guaranteeing dialysis treatment has been and remains an enormous challenge in Ukraine and we are confident that the generosity and the courage of Ukrainian dialysis staff and international aid will help to mitigate this tragic suffering.
Direct oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation and CKD G3–G5D
Authors: Welander Frida , Renlund Henrik , Dimény Emöke , Holmberg Henrik , Själander Anders
Published: January 2023

Background

The use of direct oral anticoagulants (DOAC) in patients with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD) including dialysis is growing. Several studies have shown favorable results of DOAC compared with warfarin regarding bleeding risk but no difference in stroke protection. However, these studies had poor time in therapeutic range (TTR), in the warfarin comparison group.

Methods

This was a Swedish national cohort study investigating the risk of ischemic stroke and major bleeding on DOAC compared with warfarin in patients with NVAF, glomerular filtration rate category 3–5D (G3–G5D), kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality national healthcare registries including the Swedish Renal Registry, AuriculA (the Swedish national quality register for AF and anticoagulation) and The Stroke Register.

Results

At enrolment, of 2453 patients 59% were treated with warfarin (mean TTR 67%) and 41% with DOAC. Overall, 693 (28.3%) had G3, 1113 (45.4%) G4, 222 (9.1%) G5 and 425 (17.3%) G5D. DOAC compared with warfarin showed lower hazard of major bleeding [hazard ratio 0.71 (95% confidence interval 0.53–0.96)] but no difference in ischemic stroke risk. Mortality was increased during DOAC treatment [1.24 (1.01–1.53)], presumably not a causal association since fewer fatal bleedings occurred on DOAC.

Conclusions

DOAC treatment, compared with warfarin, is associated with almost 30% lower risk of bleeding in patients with NVAF and CKD G3–G5D. The stroke risk is comparable between the treatments. This is the first study comparing DOAC and well-managed warfarin (TTR 67%) in advanced CKD. Ongoing and planned randomized controlled trials need to confirm the possible benefit of DOAC.