5-day Course Research Articles

A 5-day course of rTMS before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency.

Repetitive transcranial magnetic stimulation (rTMS) has shown promise as an intervention for pain. An unexplored research question is whether the delivery of rTMS prior to pain onset might protect against a future episode of prolonged pain. The present study aimed to determine i) whether 5 consecutive days of rTMS delivered prior to experimentally-induced prolonged jaw pain could reduce future pain intensity and ii) whether any effects of rTMS on pain were mediated by changes in corticomotor excitability (CME) and/or sensorimotor peak alpha frequency (PAF). On each day from Day 0-4, forty healthy individuals received a single session of active (n = 21) or sham (n = 19) rTMS over the left primary motor cortex. PAF and CME were assessed on Day 0 (before rTMS) and Day 4 (after rTMS). Prolonged pain was induced via intramuscular injection of nerve growth factor (NGF) in the right masseter muscle after the final rTMS session. From Days 5-25, participants completed twice-daily electronic dairies including pain on chewing and yawning (primary outcomes), as well as pain during other activities (e.g. talking), functional limitation in jaw function and muscle soreness (secondary outcomes). Compared to sham, individuals who received active rTMS subsequently experienced lower pain on chewing and yawning. Although active rTMS increased PAF, the effects of rTMS on pain were not mediated by changes in PAF or CME. This study is the first to show that rTMS delivered prior to pain onset can protect against future pain and associated functional impairment. Thus, rTMS may hold promise as a prophylactic intervention for persistent pain.

Online self-compassion training vs. expressive writing: a randomized controlled trial

ABSTRACT A number of online self-compassion trainings have emerged in recent years including the Gift of Self-Compassion (GSC), a 30-day online course. This study examined the effects of the GSC course and a modified expressive writing (EW) paradigm in a non-clinical sample. Measured outcomes were self-compassion, life satisfaction, positive and negative affect, and subjective well-being. Participants were 219 adults randomly assigned to either the GSC or EW condition. Seemingly unrelated regression models were used to estimate outcomes between groups and the relationship between curriculum usage and outcomes. Both groups demonstrated significant improvements in well-being; however, compared to EW, GSC participants reported significantly greater improvements in self-compassion. Our hypothesis that the amount of curriculum usage would impact outcomes was partially supported. The GSC course appears to be an effective online training tool that improves self-compassion skills and is at least as effective as expressive writing in enhancing subjective well-being.

Transient Ischemic Attack and Cerebral Amyloid Angiopathy-Related Inflammation: Similar Presentation, Different Entities

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare subtype of CAA characterized by a perivascular inflammatory response to amyloid deposition in the brain. The authors detail the case of a 74-year-old man with aphasia, who was diagnosed with probable CAA-ri following brain magnetic resonance imaging. Treatment recom- mendations included a 5-day course of high-dose methylprednisolone. CAA-ri may manifest with transient or permanent neurological symptoms resem- bling a transient ischemic attack or stroke, potentially leading to misdiagnosis and inadequate long-term treatment. Hence, our objective is to highlight the clinical and imaging findings of this case.

Plasmodium falciparum neonatal malaria with atypical presentation: a case series from southwestern Ethiopia

BackgroundNeonatal malaria is defined as the detection of asexual stages of Plasmodium species in the cord blood within the first 28 days of life. It can be congenital or acquired through mosquito bites or blood transfusions. Neonates are generally considered to be relatively protected due to the multiple innate and acquired physiological protective effects present in neonates. However, in areas where malaria is endemic, the prevalence of malaria in neonates is high. The predominant clinical feature of malaria in neonates is fever. Other clinical manifestations of neonatal malaria include respiratory distress, pallor and anaemia, hepatomegaly, refusal to feed, jaundice and diarrhoea. Atypical presentations without fever can lead to inaccurate diagnosis and contribute to neonatal morbidity and mortality. Neonates from endemic areas with any of the above symptoms should be screened for malaria.Case presentationWe present a series of three cases of neonatal Plasmodium falciparum malaria that presented atypically without febrile episodes and were diagnosed and managed at Mizan-Tepi University Teaching Hospital between July and September 2023. The first patient presented with vomiting, refusal to feed, pallor, severe anaemia, and splenomegaly. The second patient presented with an inconsolable cry, failure to pass feces, abdominal distention, and anaemia. The third patient presented with vomiting and anaemia. All patients received a 7-day course of intravenous artesunate; the first patient also received a blood transfusion. All patients recovered and were discharged.ConclusionsPartial immunity resulting from repeated malaria infections in endemic regions may result in the transfer of high levels of maternal Immunoglobulin G (IgG) antibodies through the placenta and can produce different atypical clinical presentations. In malaria-endemic areas, neonates presenting with any of the presenting signs and symptoms of malaria, including afebrile presentation, require malaria screening to avoid delays in diagnosis.

Experiences of Deployed Physicians in Support of Operation Allies Refuge/Operation Allies Welcome: Lessons to Inform Improvements in Training.

Stability operations, including humanitarian assistance and disaster relief missions, are key functions of U.S. Military medicine and the Military Medical Humanitarian Assistance Course (MMHAC) is a 2-day course widely used to prepare military medical personnel for such missions. It focuses on caring for those most vulnerable in the wake of disasters, particularly children. The large-scale humanitarian deployment of military medical providers in support of Operation Allies Welcome/Operation Allies Refuge (OAW/OAR) presents an opportunity to evaluate the preparedness of these providers to care for the needs of the Afghan travelers, so we explored the experiences of military medical providers deployed in support of OAW/OAR to inform improvements in the MMHAC. We conducted a qualitative study of military medical providers who were deployed in support of OAW/OAR using a series of three virtual focus groups. Focus group questions were structured around the main topics covered in the MMHAC (patient care, ethical considerations, logistical concerns, and preventive and public health) and explicitly asked about adaptive leadership challenges faced and strategies used to overcome them. We analyzed transcripts using inductive thematic analysis within a constructivist paradigm, with adaptive leadership as a sensitizing concept. The study was approved by the Institutional Review Board of Uniformed Services University. We constructed 4 themes from participant responses, each addressing challenges that medical providers faced during their mission: (1) Medical providers navigated tension between medical and public health priorities and military mission priorities; (2) Chronic and complex care needs posed unique challenges for medical personnel; (3) Challenges in patient care were compounded by logistical and system-based barriers; and (4) Cultural barriers led to ethical dilemmas that physicians felt inadequately prepared to handle, most notably with respect to gender-related concerns. Within each theme, participants described which aspects of MMHAC training were most helpful and which areas were inadequate. Physicians found the OAR/OAW mission meaningful but also identified challenges related to medical care provision, public health, logistics, and ethical dilemmas that hindered their ability to carry out their medical mission. Lessons learned from OAW/OAR highlight several areas in which the MMHAC training could be augmented and improved to further mitigate these challenges.

A Pilot and Feasibility Study to Evaluate the Effectiveness of Tofacitinib Add-On Therapy to Remdesivir in Severely Ill COVID-19 Patients.

This placebo-controlled and randomized pilot study aimed to assess the feasibility and impact of tofacitinib/remdesivir combination therapy compared to remdesivir alone on clinical and laboratory findings of severely ill COVID-19 patients for future large-scale studies. Fifty patients were included in this study. They were randomly allocated into two groups of 25 subjects each. Patients in the treatment group received a five-day course of tofacitinib (10 mg twice daily) in addition to a five-day course of remdesivir, whereas the control group received a 10-day course of remdesivir with a placebo. There was no significant difference in rates of need for intubation (oxygen saturation level), intensive care unit (ICU) admission, death and length of hospitalization between the two groups (P>0.05). Nevertheless, the PRIEST severity score was significantly reduced in the treatment group compared to the control group (P=0.03, effect size [95% CI]: -0.616 [0.0233-1.1723]). Moreover, the mean level of C-reactive protein after 10 days was significantly decreased in the treatment group but increased in the control group (P=0.006). Tofacitinib adopted in this pilot study modulate the inflammation and reduce the PRIEST score in severe COVID-19 patients. So, it is feasible and could be applied in future larger-scale trials to precisely determine its effects on coronavirus infections.

Selective decontamination of the digestive tract in a burns unit reduces the incidence of hospital-acquired infections: A retrospective before-and-after cohort study

ObjectiveTo evaluate the effect of selective decontamination of the digestive tract (SDD) on hospital-acquired infections (HAIs) in patients with acute burn injury requiring admission to a Burns Unit (BU). DesignRetrospective before-and-after cohort study, between January 2017 and June 2023. SDD was implemented in March 2019, dividing patients into two groups. SettingFour-bed BU, in a referral University Hospital in Spain. PatientsAll the patients admitted during the study period were eligible for analysis. Patients who died or were discharged within 48hours of admission, and patients with an estimated survival less than 10% not considered for full escalation of therapy were excluded. InterventionSDD comprised the administration of a 4-day course of an intravenous antibiotic, and an oral suspension and oral topical paste of non-absorbable antibiotics during the stay in the BU. Main variable of interestIncidence of HAIs during the stay in the BU. Secondary outcomes: incidence of specific types of infections by site (bacteremia, pneumonia, skin and soft tissue infection) and microorganism (Gram-positive, Gram-negative, fungi), and safety endpoints. ResultsWe analyzed 72 patients: 27 did not receive SDD, and 45 received SDD. The number of patients who developed HAIs were 21 (77.8%) and 21 (46.7%) in the non-SDD and the SDD groups, respectively (p=0.009). The number of hospital-acquired infectious episodes were 2.52 (1.21–3.82) and 1.13 (0.54–1.73), respectively (p=0.029). ConclusionsSDD was associated with a reduced incidence of bacterial HAIs and a decrease in the number of infectious episodes per patient.

Unilateral hindlimb ischaemia-induced systemic inflammation is associated with non-ischaemic skeletal muscle inflammation.

Skeletal muscle atrophy and dysfunction commonly accompany cardiovascular diseases such as peripheral arterial disease and may be partially attributable to systemic inflammation. We sought to determine whether acute systemic inflammation in a model of hindlimb ischaemia (HLI) could affect skeletal muscle macrophage infiltration, fibre size, or capillarization, independent of the ischaemia. Eight-week-old C57BL/6 male mice underwent either Sham or HLI surgery, and were killed 1, 3, or 7 days post-surgery. Circulating inflammatory cytokine concentrations were measured, as well as immune cell infiltration and morphology of skeletal muscle from both limbs of HLI and Sham mice. In HLI compared with Sham mice at day 1, plasma interleukin-1β levels were 216% higher (0.48±0.10 vs. 0.15±0.01pg/μL, P = 0.005) and decreased by day 3. This was followed by increased macrophage presence in muscle from both ischaemic and non-ischaemic limbs of HLI mice by day 7 (7.3- and 2.3-fold greater than Sham, respectively, P<0.0001). In HLI mice, muscle from the ischaemic limb had 21% lower fibre cross-sectional area than the non-ischaemic limb (724±28 vs. 916±46μm2, P = 0.01), but the non-ischaemic limb of HLI mice was no different from Sham. This shows that HLI induces acute systemic inflammation accompanied by immune infiltration in both ischaemic and remote skeletal muscle; however, this did not induce skeletal muscle atrophy in remote muscle within the 7-day time course of this study. This effect of local skeletal muscle ischaemia on the inflammatory status of remote skeletal muscle may signal a priming of muscle for subsequent atrophy over a longer time course. HIGHLIGHTS: What is the central question of this study? Does hindlimb ischaemia-induced inflammation cause acute immune, inflammatory and morphological alterations in remote non-ischaemic skeletal muscle? What is the main finding and its importance? Hindlimb ischaemia induced systemic inflammation with subsequent neutrophil and macrophage infiltration in both ischaemic and non-ischaemic skeletal muscle; however, morphological changes did not occur in non-ischaemic muscle within 7 days. These immune alterations may have functional implications that take longer than 7 days to manifest, and subsequent or prolonged systemic inflammation and immune infiltration of muscle could lead to morphological changes and functional decline.

Impact of a 1-day disease overview session on knowledge and preparedness for incoming hematology/oncology fellows.

e21011 Background: The start of hematology/oncology fellowship involves an abrupt transition in disease management and a steep learning curve. Many fellowship programs have introductory lecture series over the first weeks or months, but fellows often need specialty knowledge prior to the completion of these. Methods: A 1-day session for incoming first year fellows at our institution was developed to provide brief overviews of common conditions in classical hematology, malignant hematology, and oncology, subdivided into a total of 12 topics. Fellows were surveyed before and after the session regarding their feelings of preparation for fellowship and having good disease frameworks for each of the 3 major content areas. Fellows also evaluated the content and length of each topic. Pre- and post-course knowledge assessments were conducted. Feedback was sought later in the year as well. Results: The session was well-received by fellows. Post-course assessments increased by a mean of 32% (SD 6%). The majority of topics were well-reviewed for length and content. Fellow responses to feelings of preparedness and disease frameworks were improved or unchanged from pre-course surveys. All fellows agreed that it was a good use of their time and would recommend it being a part of future orientation sessions. Fellows recommended splitting the session into 2 days. Conclusions: A 1-day introductory course for incoming hematology/oncology fellows is feasible and rapidly improves baseline knowledge to prepare fellows for clinics, consults, and being on call.

Clinical outcomes and safety of remdesivir in hospitalized individuals with COVID-19, with or without severe renal impairment

BackgroundThe use of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal impairment has been approved; however, limited clinical data exist. Accordingly, we aimed to compare outcomes and adverse events associated with remdesivir in hospitalized patients with COVID-19, with and without severe renal impairment. MethodsHospitalized patients with COVID-19 undergoing a 5-day remdesivir course at Taipei Veterans General Hospital from April 1 to July 31, 2022, were enrolled. Comparative analysis of outcomes and safety between patients with or without severe renal impairment (estimated glomerular filtration rate of < 30 mL/min per 1.73 m2) were conducted. Prognostic factors associated with 28-day mortality in patients with severe renal impairment were investigated using logistic regression analysis. ResultsA total of 671 hospitalized patients, including 132 patients with severe renal impairment, who received a 5-day course of remdesivir were analyzed. The 28-day mortality was higher in patients with severe renal impairment than in patients without severe renal impairment (15.2% vs. 7.8%). The proportion of patients with acute kidney injury (AKI) and deteriorated liver function after completing remdesivir therapy was similar between the patients with and without severe renal impairment, and the recovery rate of AKI was similar in both groups. The sequential organ failure assessment score was an independent factor associated with 28-day mortality in patients with severe renal impairment. ConclusionsRemdesivir was well-tolerated in hospitalized patients with COVID-19, regardless of renal function. Our findings support the recent recommendation to administer remdesivir in patients with severe renal impairment.

Trismus caused by migration of orthodontic archwire into the infratemporal fossa: a case report.

Soft tissue injuries are known complications of orthodontic treatment. Most of the injuries are mild, but severe complications can arise from deeper penetration or dislodgement of brackets and other foreign bodies into the surrounding tissues of the oropharynx and infratemporal fossa. The patient, accompanied by his parents, presented to the Children's Emergency Department with the concern of gradual limitation of mouth opening and eventual trismus, which occurred over a span of 2 weeks. The patient presented with trismus and slight discomfort at the left cheek region. He reported a history of gradual limitation to his mouth opening 2 weeks prior. He was wearing upper and lower fixed orthodontic appliances and the left distal end of the maxillary archwire was found to have migrated into the left infratemporal fossa. Left medial pterygoid muscle inflammation, or bleeding and haematoma formation, or infection within the infratemporal region. The maxillary archwire was removed in the Children's Emergency Department and a computed tomography (CT) scan performed subsequently confirmed the diagnosis of left medial pterygoid muscle inflammation. The patient was started on an intravenous (IV) antibiotic and a 2-day course of IV dexamethasone to reduce the muscle inflammation. By the second day, the patient was able to achieve a mouth opening of 6 mm, and by the second week, the mouth opening had returned to normal. The potential risk of soft tissue injury and complications from orthodontic treatment is generally mild and limited. Soft tissue injuries can be avoided with careful management by the operator with the proper precautions taken. Clinicians should be familiar with the surrounding soft tissue anatomy and be aware of the potential for more severe complications and provide management or referral to the appropriate specialty accordingly.

Motivational interviewing from the paediatricians’ perspective: assessments after a 2-day training for physicians caring for adolescents with chronic medical conditions (CMCs)

BackgroundCounselling adolescents with chronic medical conditions (CMCs) can be challenging regarding suitable interviewing skills and clinicians’ attitudes toward the patient. Successful communication can be a key element of treatment. Motivational Interviewing (MI) is broadly applicable in managing behavioural problems and diseases by increasing patient motivation for lifestyle changes. However, data concerning the applicability, feasibility and implementation of MI sessions in everyday practice are missing from the physicians’ point of view.MethodThe present study was conducted as a mixed methods design. Twenty paediatricians were randomized to a 2-day MI course followed by MI consultations. Data were collected through a questionnaire one year after MI training. Factors for effective training and possible barriers to successful use of MI were examined.ResultsCompleted questionnaires were returned by 19 of 20 paediatricians. The paediatricians’ experiences with MI demonstrate that MI is regarded as a valuable tool when working with adolescents with CMCs. 95% of all respondents reported that they found MI education necessary for their clinical work and were using it also outside the COACH-MI study context. 73.7% percent saw potential to strengthen the connection to their patients by using MI. The doctors were already using more MI conversation techniques after a 2-day MI course. Obstacles were seen in the short training, the lack of time and missing undisturbed environment (interruptions by telephone, staff, etc.) during clinical flow.ConclusionsMI techniques are not yet a regular part of medical training. However, a 2-day MI course was rated effective and provided a lasting impact by physicians caring for children and adolescents with chronic medical conditions (CMCs), although booster sessions should be offered regularly.Trial registrationThe study was registered in the German Clinical Trials Register (DRKS00014043) on 26/04/2018.

Case Report: Effect of rTMS on urinary incontinence in major vascular neurocognitive disorder

Background Urinary incontinence (UI) was an intractable symptom and many efforts had been made to combat this symptom over the past decades. Repetitive transcranial magnetic stimulation (rTMS) was used in many diseases for its focusing on neural network regulation. However, rTMS on the cortical urination center for acting on urination process remained further study. Case report A 67-year-old female farmer suffered from UI over two weeks. She was diagnosed with major vascular neurocognitive disorder. The patient received rTMS on the bilateral paracentral lobule. Stimulation was administered at 20 Hz with 25 stimulation trains of 30 stimuli each with a 30-second intertrain interval. After a 5-day course of rTMS intervention, the patient reported full awareness of her urination, but her neurocognitive decline had not improved at all. Conclusions In this case of UI with major vascular neurocognitive disorder, rTMS on the bilateral paracentral lobule was applied and therapeutic effect on UI was obvious.

Post-exposure HIV prophylaxis adherence to full 28-day course versus weekly therapy in Tehran

Post-exposure HIV prophylaxis adherence to full 28-day course versus weekly therapy in Tehran

Abstract B014: FGFR inhibition upregulates Nectin-4 expression in FGFR3 altered urothelial carcinoma

Abstract Bladder urothelial carcinoma (UC) is a common malignancy and remains a significant cause of mortality; however, in recent years there have been substantial advances in the treatment of metastatic UC (mUC). This includes the approval of the antibody drug conjugate (ADC) enfortumab vedotin, which targets Nectin-4, and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib (in FGFR2/3 altered tumors). Despite the impressive efficacy of these agents, most patients will ultimately develop progressive disease, underlining the need for further therapeutic development. Previous work has demonstrated that NECTIN4 expression and FGFR3 alterations are enriched in luminal subtypes of UC and NECTIN4 expression is higher in FGFR altered tumors. We validate these findings in scRNAseq from primary tumors as well as bulk RNAseq from murine models. Given the positive correlation between NECTIN4 and FGFR3 alterations we hypothesized that FGFR3 inhibition would downregulate Nectin-4 expression. To our surprise we found in vitro treatment with erdafitinib in cell lines with FGFR3 fusion proteins (RT112, RT4, SW780) lead to an increase in Nectin-4 protein levels. Additionally, in vitro FGFR inhibition in the UMUC-14 cell line which harbors an FGFR3S249C hotspot mutation, upregulates Nectin-4 protein levels. To further investigate this phenomenon, we engineered the FGFR3 WT cell line, 5637 to overexpress FGFR3-TACC3 or FGFR3S249C. We saw that FGFR3-TACC3 and FGFR3S249C overexpression both down regulated Nectin-4 indicating that FGFR3 activity negatively regulates Nectin-4 expression. We have also investigated the association between FGFR inhibition and Nectin-4 expression in two in vivo models: (1) in a xenograft model using the RT112 line we found an overall increase in Nectin-4 expression in tumors treated with a 5-day course of erdafitinib; (2) in a UPFL1 (a cell line derived from a genetically engineered mouse with a S249C mutation) syngeneic model we also saw an increase in Nectin-4 expression after erdafitinib treatment. We have observed that the increase in Nectin-4 expression persists in vitro even after withdrawal of erdafitinib treatment, indicating that intermittent dosing of erdafitinib maybe be sufficient to prime a tumor for Nectin-4 targeted therapy. Lastly, preliminary in vitro investigation of the combination of erdafitinib and enfortumab vedotin in RT112 cells showed synergy, particularly with lower doses of both agents, providing further support of our hypothesis that FGFR3 inhibition may act to sensitize UC to Nectin-4 ADC therapy. A potential synergistic relationship is further supported by the recent results of the phase 1 trial investigating the combination of erdafitinib plus enfortumab vedotin in which the objective response rate was 100% (9/9 patients: 8 PRs &amp; 1CR). Citation Format: Sean Clark-Garvey, Mi Zhou, Michael Sturdivant, Wolfgang Beckabir, Lucia Kim, E. Drew Toomer, Ian McCabe, Akihiro Hamada, Daniel Crona, Jeffrey S. Damrauer, William Y. Kim. FGFR inhibition upregulates Nectin-4 expression in FGFR3 altered urothelial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B014.

Zuranolone Concentrations in the Breast Milk of Healthy, Lactating Individuals: Results From a Phase 1 Open-Label Study.

Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid type A receptors and a neuroactive steroid approved as an oral, once-daily, 14-day treatment course for adults with postpartum depression in the United States. This study assessed zuranolone transfer into breast milk. Healthy, nonpregnant, lactating adult female participants received once-daily 30 mg zuranolone from day (D)1 through D5 in this phase 1 open-label study. The relative infant dose (RID; weight-adjusted proportion of the maternal dose in breast milk over 24 hours) for 30 mg zuranolone was assessed at D5. An RID for 50 mg zuranolone was estimated using a simulation approach across a range of infant ages and weights. Of 15 enrolled participants (mean age, 30.1 years), 14 completed the study. The mean RID for 30 mg zuranolone at D5 was 0.357%; the mean steady-state milk volume over D3 to D5 decreased from baseline by 8.3%. Overall unbound zuranolone in plasma was low (≤0.49%). Plasma concentrations peaked at D5 before decreasing in a biexponential manner. There was strong concordance between the temporal profiles of zuranolone concentrations in plasma and breast milk. The estimated mean RID for 50 mg zuranolone based on a milk intake of 200 mL/kg per day was 0.984%. All treatment-emergent adverse events reported by participants were mild, the most common being dizziness (n = 3). Zuranolone transfer into the breast milk of healthy, nonpregnant, lactating adult female participants was low; the estimated RID for 50 mg zuranolone was <1%, well below the <10% threshold generally considered compatible with breastfeeding.

High-frequency photoacoustic and ultrasound imaging for skin evaluation: Pilot study for the assessment of a chemical burn.

Skin architecture and its underlying vascular structure could be used to assess the health status of skin. A non-invasive, high resolution and deep imaging modality able to visualize skin subcutaneous layers and vasculature structures could be useful for determining and characterizing skin disease and trauma. In this study, a multispectral high-frequency, linear array-based photoacoustic/ultrasound (PAUS) probe is developed and implemented for the imaging of rat skin in vivo. The study seeks to demonstrate the probe capabilities for visualizing the skin and its underlying structures, and for monitoring changes in skin structure and composition during a 5-day course of a chemical burn. We analayze composition of lipids, water, oxy-hemoglobin, and deoxy-hemoglobin (for determination of oxygen saturation) in the skin tissue. The study successfully demonstrated the high-frequency PAUS imaging probe was able to provide 3D images of the rat skin architecture, underlying vasculature structures, and oxygen saturation, water, lipids and total hemoglobin.

Genetic variations of penicillin-binding protein 1A: insights into the current status of amoxicillin-based regimens for Helicobacter pylori eradication in Malaysia.

Introduction. Resistance towards amoxicillin in Helicobacter pylori causes significant therapeutic impasse in healthcare settings worldwide. In Malaysia, the standard H. pylori treatment regimen includes a 14-day course of high-dose proton-pump inhibitor (rabeprazole, 20 mg) with amoxicillin (1000 mg) dual therapy.Hypothesis/Gap Statement. The high eradication rate with amoxicillin-based treatment could be attributed to the primary resistance rates of amoxicillin being relatively low at 0%, however, a low rate of secondary resistance has been documented in Malaysia recently.Aim. This study aims to investigate the amino acid mutations and related genetic variants in PBP1A of H. pylori, correlating with amoxicillin resistance in the Malaysian population.Methodology. The full-length pbp1A gene was amplified via PCR from 50 genomic DNA extracted from gastric biopsy samples of H. pylori-positive treatment-naïve Malaysian patients. The sequences were then compared with reference H. pylori strain ATCC 26695 for mutation and variant detection. A phylogenetic analysis of 50 sequences along with 43 additional sequences from the NCBI database was performed. These additional sequences included both amoxicillin-resistant strains (n=20) and amoxicillin-sensitive strains (n=23).Results. There was a total of 21 variants of amino acids, with three of them located in or near the PBP-motif (SKN402-404). The percentages of these three variants are as follows: K403X, 2%; S405I, 2% and E406K, 16%. Based on the genetic markers identified, the resistance rate for amoxicillin in our sample remained at 0%. The phylogenetic examination suggested that H. pylori might exhibit unique conserved pbp1A sequences within the Malaysian context.Conclusions. Overall, the molecular analysis of PBP1A supported the therapeutic superiority of amoxicillin-based regimens. Therefore, it is crucial to continue monitoring the amoxicillin resistance background of H. pylori with a larger sample size to ensure the sustained effectiveness of amoxicillin-based treatments in Malaysia.

Doxycycline adherence for the management of Chlamydia trachomatis infections

BackgroundThe updated 2021 CDC treatment guidelines recommend a single dose of 500 mg intramuscular ceftriaxone for Neisseria gonorrhea and doxycycline 100 mg by mouth twice daily for 7 days for Chlamydia trachomatis coinfection. However, there is a significant public health concern regarding patient non-adherence to the 7-day course of doxycycline. To date, there are no studies assessing this concern. Therefore, the objective of this study was to evaluate a patient's adherence to doxycycline for chlamydial infections after discharge from the Emergency Department (ED). MethodsThis was an IRB-approved, single-center, retrospective cohort study evaluating the adherence to doxycycline for Chlamydia trachomatis infections. Patients who received treatment and were discharged from the ED with a doxycycline e-prescription between May 2021 and September 2022 were included. Patients were excluded if <18 years of age, pregnant, a sexual assault victim, or admitted inpatient. The primary endpoint was the incidence of doxycycline prescription pick-up after discharge from the ED. The secondary endpoint was the incidence of repeat ED visits for the same chief complaint within 28 days. Descriptive statistics were computed for all study variables and Fisher's Exact tests were used to assess the outcomes. ResultsA review of 144 patients who tested positive for chlamydia and were discharged from the ED with an e-prescription for doxycycline revealed that 18% of patients did not pick up their prescription (N = 26). Non-adherent patients were more likely to return to the ED with the same chief complaint within 28 days (23.1% vs 7.6%, OR 3.6 [1.2–11.3], p = 0.026). No differences were detected in baseline demographics, housing status, insurance type, sexual orientation, or Sexually Transmitted Infection history. ConclusionFor patients with a positive chlamydia infection who were discharged from the ED on doxycycline, an 18% non-adherence rate was found and a 3.6-fold higher likelihood of returning to the ED with the same chief complaint if the prescription was not picked up.

From training to practice: long-term perspectives of graphic facilitation used in organisations

ABSTRACT Graphic facilitation is a growing international practice and is often used to describe what professionals do when visually facilitating group processes. Although the professional arena has grown, there is a lack of empirical research in the field, especially regarding long-term perspectives on applying the practice in organisations. This paper aims at investigating employees’ experiences and competence development over time within graphic facilitation. The study followed three employees, first in a 2-day basic graphic facilitation course, then in follow-up interviews, eight months, and two years after completing the course. The empirical data were analysed based on a literature review conducted on long-term perspectives, focusing on three themes: 1. The graphic facilitation practice at individual, group, and organisational level; 2. Contextual knowledge and knowing about the participants; 3. Relation between objects, processes and competencies needed. The findings show that all three employees from different organisations continued to use graphic facilitation and found it valuable for giving new insights and overviews of processes and tasks. The methods aided in creating common ground and goals. The employees activated their contextual organisational knowledge to aid the process and found that being sensitive to various groups’ needs and personal preferences were effective when applying the methods.