Case Report: Optimum excision with split skin graft closure in the management of penile sebaceous carcinoma.

Sebaceous carcinoma (SC) is a rare malignant skin neoplasm derived from the meibomian gland of adnexal epithelium, which is frequently confused with basal cell carcinoma (BCC), exhibiting sebaceous differentiation and commonly found in the head and neck regions. We report a case of penile sebaceous carcinoma, an extremely rare anatomical site for SC. A 68-year-old man presented with a 4-month history of painless, non-healing ulcerated nodules over the left side of the penile shaft. Wedge biopsy showed adenocarcinoma with signet ring differentiation. We proceeded with wide local excision (WLE) of the lesion with the inclusion of the indurated skin and 5 mm of normal margin, followed by primary closure of the scrotal defect and split skin grafting of the penile shaft by using a thigh skin donor. The final histopathological examination revealed sebaceous carcinoma with pagetoid spread. The patient achieved recurrence-free survival without any form of adjuvant therapy after 4 years of follow-up.

Performance of Point-of-Care Ultrasonography in Confirming Feeding Tube Placement in Mechanically Ventilated Patients.

BACKGROUND: A feeding tube (FT) is routinely placed in critically ill patients, and its correct placement is confirmed with a chest X-ray (CXR), which is considered the gold standard. This study evaluated the diagnostic accuracy of ultrasonography (USG) in verifying FT placement compared to a CXR in an intensive care unit (ICU). METHOD: This was a prospective single-blind study conducted on patients admitted to the ICU of a tertiary hospital in Malaysia. The FT placements were verified through a fogging test and USG at the neck and subxiphoid points. The results of confirmation of FT placement through USG were compared with those obtained using CXRs. RESULTS: A total of 80 patients were included in this study. The FT positions were accurately confirmed by overall USG assessments in 71 patients. The percentage of FT placements correctly identified by neck USG was 97.5%, while the percentage of those identified by epigastric USG was 75%. The corresponding patients' CXRs confirmed correct FT placement in 76 patients. The overall USG assessment had a sensitivity of 92.11% and specificity of 75%, a positive predictive value of 98.59%, and a negative predictive value of 33.33%. The USG findings also showed a significant association between FT size and BMI. FTs with a size of 14Fr were better visualized (p = 0.008), and negative USG findings had a significantly higher BMI (p < 0.001). CONCLUSION: USG is a simple, safe, and reliable bedside assessment that offers relatively high sensitivity in confirming correct FT placement in critically ill patients.

Embedded information of aerosol type, hygroscopicity and scattering enhancement factor revealed by the relationship between PM2.5 and aerosol optical depth.

Satellite aerosol optical depth (AOD) provides an alternative way to depict the spatial distribution of near-surface PM2.5. In this study, a mathematical formulation of how PM2.5 is related to AOD is presented. When simplified to a linear equation, a functional dependence of the slope on the aerosol type, scattering enhancement factor f(RH), and boundary layer height is revealed, while the influence of the vertical aerosol profile is embedded in the intercept. Specifically, we focus on the effects of aerosol properties and employ a new aerosol index (Normalized Gradient Aerosol Index, NGAI) for classifying aerosol subtypes. The combination of AOD difference at shorter wavelengths over longer-wavelength AOD from AERONET data could distinguish and subclassify aerosol types previously indistinguishable by AE (i.e., urban-industrial pollution, U/I, and biomass burning, BB). AOD-PM2.5 regressions are performed on these aerosol subtypes at various relative humidity (RH) levels. The results suggest that BB aerosols are nearly hydrophobic until the RH exceeds 80 %, while the AOD-PM2.5 regressions for U/I depend on RH levels. Moreover, the scattering enhancement factor f(RH) can be calculated by taking the ratio of intercepts between dry and humidity conditions, which is proposed and tested for the first time in this study. Our results show an f(RH ≥ 80 %) of ∼2.6 for U/I-dominated aerosols, whereas the value is not over 1.5 for BB aerosols. The f(RH) can be further used to derive the optical hygroscopicity parameter (κsca), demonstrating that the NGAI can be used to exploit differences in aerosol hygroscopicity and improve the AOD-PM2.5 relationship.

The effects of hydrogen treatment in a cigarette smoke solution-induced chronic obstructive pulmonary disease-like changes in an animal model.

Background: Molecular hydrogen, with its antioxidant and anti-inflammatory properties, may be suitable for the prevention and treatment of chronic obstructive pulmonary disease (COPD). This study aims to investigate the therapeutic efficacy of hydrogen-oxygen (H2/O2) treatment in cigarette smoke solution (CSS)-induced COPD-like injury in a female BALB/c mouse model. Methods: Thirty mice were randomly assigned to three groups: Control (n=8), COPD (n=10), and COPD + H2/O2 (n=12). CSS was administered by intraperitoneal (IP) injection twice weekly for 6 weeks during the COPD induction phase. Simultaneously, the COPD + H2/O2 group started received 75 minutes of inhalation therapy (42% H2) delivered by the Oxy-Hydrogen Generator twice daily for 9 weeks. Mice body weights and survival were measured throughout the study period. Neutrophil elastase (NE) activity and lung histopathological changes were also evaluated. Results: The results showed a higher survival rate in the COPD + H2/O2 group compared to the COPD group (100% vs. 80%) during the induction phase. Slight decreases in body weight gains were observed in the COPD and COPD + H2/O2 groups during the first 15 days of the induction phase, but there was no significant difference in mean body weights among the three groups throughout the study period. NE activity was numerically lower in the COPD + H2/O2 group compared to the COPD group. The histopathological evaluation showed significant improvements in the H2/O2-treated mice with respect to mean linear intercept (MLI) and lesion (inflammation and emphysema) scores. Improvements in goblet cell hypertrophy and hyperplasia of airway epithelium were not significant. Conclusions: A 9-week H2/O2 inhalation therapy delivered by the Oxy-Hydrogen Generator to CSS-induced COPD-like injury in mice showed improvement in survival rate, alveolar structural changes, and histopathological lesion scores of the lung.

Prospective Evaluation of Pain and Anxiety Levels Between Wide-Awake Local Anesthesia No Tourniquet and General Anesthesia With Tourniquet in Excision of Wrist Ganglions.

Purpose: Excision of wrist ganglions is a common procedure in hand surgery. Our objective was to determine whether the type of anesthesia (general anesthesia [GA] vs wide-awake local anesthesia no tourniquet [WALANT] technique) would affect patient satisfaction regarding intraoperative pain control, postoperative pain management, and anxiety. Methods: This was a prospective study with patients divided into either the WALANT or GA cohort. The waiting time for surgery, Amsterdam Preoperative Anxiety and Information Scale, blood pressure, and heart rate were measured. Postsurgical questionnaires with the visual analog scale were completed. The surgeon's feedback on the ease of ganglion stalk visibility and usage of diathermy as a measure of a bloodless field was recorded. Patients reported the amount of analgesia consumed and overall satisfaction with the operation via the Surgical Satisfaction-8 questionnaire. Results: A total of 42 patients underwent wrist ganglion excision in 2 orthopedic centers over a period of 2 years, with 21 undergoing GA and 22 undergoing WALANT. The GA group was more anxious about anesthetic use with a higher demand for information about GA (P = .04). The duration of surgery was significantly shorter in the WALANT group and with a lower diathermy usage (P < .001). There was no difference in terms of surgical difficulty and stalk visualization. The visual analog scale pain score was significantly lower in the WALANT group than in the GA group immediately after surgery (P = .04) and on discharge (P = .004). While at home for 2 weeks, the WALANT group (mean = 2.91 tablets) consumed significantly fewer analgesic tablets than the GA group (mean = 6.25 tablets). However, both groups were satisfied with their experience. Conclusions: Wide-awake local anesthesia no tourniquet technique in the excision of ganglions provides another option of anesthesia with painless experiences, and no pain rebound after surgery. Patients were less anxious about WALANT than GA. Excision can be performed without diathermy usage with similar visualization of the stalk. Type of study/level of evidence: Therapeutic II.

Intravenous fentanyl vs. topical lignocaine for ProSeal™ laryngeal mask airway insertion with propofol induction.

Insertion of the laryngeal mask airway (LMA) without muscle relaxant requires adequate obtundation of airway reflexes, which may otherwise lead to incorrect or failed LMA placement. This study compared topical lignocaine spray vs. intravenous (IV) fentanyl, during propofol induction for insertion of the ProSeal™ LMA (PLMA). This was a prospective, randomized, double blind study, in ASA I or II patients, for elective or emergency surgery. Seventy patients (n = 70) who fulfilled the inclusion criteria were randomly assigned to receive IV fentanyl 2 mcg/kg or topical lignocaine spray 40 mg, prior to anesthesia induction with IV propofol (2-2.5 mg/kg). ProSeal™ LMA insertion condition was regarded optimal in the absence of adverse responses (gag, cough, laryngospasm and body movements), and successful LMA placement at the first attempt. Hemodynamic parameters were recorded and patients were assessed for sore throat and hoarseness post operatively. Seventy patients were analyzed. The number of patients with optimal PLMA insertion conditions were comparable between the groups (60% vs. 57%, P = 0.808). All hemodynamic parameters were comparable between groups with the exception of heart rate. Sympathetic obtundation of heart rate was greater with IV fentanyl than topical lignocaine (P < 0.05). The proportion of patients with postoperative sore throat significantly increased with the number of insertion attempts (P < 0.05). Topical lignocaine spray to the pharynx is as effective, and may be an alternative to IV fentanyl, during propofol induction for PLMA insertion. Success rate and optimal insertion condition at the first attempt, propofol requirement, blood pressure, adverse events and airway complications were comparable. Heart rate obtundation was less with topical lignocaine spray but remained within clinically acceptable values.

Clinical Performance Comparison of LMA Protector™ Cuff Pilot™ and LMA Supreme™ When Used in Anesthetized, Non-paralyzed Patients.

Introduction The advancement of supraglottic airways (SGAs) has eased airway management, especially for anesthetists. There were functional improvements implemented to the newer SGA. We aim to assess the clinical performance of laryngeal mask airway (LMA) Protector™ Cuff Pilot™ (Teleflex Inc., Wayne, Pennsylvania, USA) against LMA Supreme™ (Teleflex Inc., Wayne, Pennsylvania, USA), in terms of oropharyngeal leak pressure (OLP), successful insertion attempts, mean insertion time, ease of gastric tube insertion, laryngeal view, and incidence of sore throat among anesthetized, non-paralyzed patients undergoing general anesthesia. Methods In this prospective single-blinded study, 60 patients were randomized to use either LMA Protector™ Cuff Pilot™ or LMA Supreme™. Both groups received standard monitoring and induction regimes. Post-insertion, a bronchoscope was used to verify its position. A gastric tube was inserted and OLP was measured. Patients were assessed during the post-operative period for sore throats. Results LMA Protector™ Cuff Pilot™ was comparable to LMA Supreme™ in terms of mean OLP (30.72±8.60 vs 27.23±8.09 cmH2O, P = 0.114), first successful attempt (P = 0.312), mean insertion time (27.72±9.45 vs 24.37±6.46 seconds, P = 0.116), and grade 1 laryngeal view (51.7% vs 36.7%, P = 0.244). At first attempt, LMA Protector™ Cuff Pilot™ had a lower success rate of gastric tube insertion than LMA Supreme™ (55.17% vs 96.67%, P <0.001). The incidence of the blood-stained device and sore throat post-operatively were comparable between the two groups. Conclusion LMA Protector™ Cuff Pilot™ was comparable to LMA Supreme™ in terms of overall clinical performance, except for the first successful gastric tube insertion. Improvements should be made to the gastric channel for easier gastric tube insertion in the LMA Protector™ Cuff Pilot™.

Validation of the Malay Self-Report Quick Inventory of Depressive Symptomatology in a Malaysian Sample.

Depression is ranked as the second-leading cause for years lived with disability worldwide. Objective monitoring with a standardized scale for depressive symptoms can improve treatment outcomes. This study evaluates the construct and concurrent validity of the Malay Self-Report Quick Inventory of Depressive Symptomatology (QIDS-SR16) among Malaysian clinical and community samples. This cross-sectional study was based on 277 participants, i.e., patients with current major depressive episode (MDE), n = 104, and participants without current MDE, n = 173. Participants answered the Malay QIDS-SR16 and were administered the validated Malay Mini-International Neuropsychiatric Interview (MINI) for DSM-IV-TR. Factor analysis was used to determine construct validity, alpha statistic for internal consistency, and receiver operating characteristic (ROC) analysis for concurrent validity with MINI to determine the optimal threshold to identify MDE. Data analysis provided evidence for the unidimensionality of the Malay QIDS-SR16 with good internal consistency (Cronbach's α = 0.88). Based on ROC analysis, the questionnaire demonstrated good validity with a robust area under the curve of 0.916 (p < 0.000, 95% CI 0.884−0.948). A cut-off score of nine provided the best balance between sensitivity (88.5%) and specificity (83.2%). The Malay QIDS-SR16 is a reliable and valid instrument for identifying MDE in unipolar or bipolar depression.

A Randomized Controlled Trial Comparing Wide-Awake Local Anesthesia With No Tourniquet (WALANT) to General Anesthesia in Plating of Distal Radius Fractures With Pain and Anxiety Level Perception.

INTRODUCTION: Distal end radius fractures are common fractures commonly treated with an option of open reduction and plating. Traditionally, plating is performed under general anesthesia (GA) or regional block. Recently, a new technique of plating under wide-awake local anesthesia with no tourniquet (WALANT) has been introduced. We aim to compare the preoperative anxiety level, intraoperative pain scores, post-operative pain scores, operating time, blood loss and clinical outcome of distal end radius plating with WALANT versus GA with tourniquet. METHODS: We conducted a randomized controlled study on patients with closed fracture of the distal end of the radius requiring open reduction and plating from January 2019 till April 2020. We recruited 65 patients (33 patients in the WALANT group and 32 patients in the GA group). Randomization was done via block randomization. Data were collected to evaluate preoperative anxiety using the Amsterdam Preoperative Anxiety and Information Scale (APAIS) score, intraoperative pain score during injection (baseline) (V1), 10 minutes after injection (V2), during incision (V3), during gentle manipulation (V4), during aggressive manipulation (V5) and during first drilling of screw (V6), blood loss, duration of surgery and post-operative pain score. Additionally, intraoperative visual analog scale (VAS) score was obtained in the WALANT group. At three weeks, six weeks, three months and six months after operation, the Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) scores and range of motion (ROM) of the wrists were obtained. RESULTS: The average age in the WALANT group was 47.19 (range, 36-64) years and GA group was 49.48 (range, 38-60) years. The mean APAIS score obtained was 7.78 (WALANT group) and 7.36 (GA group) with no statistical difference. For intraoperative VAS, only during V4 and V5 were the scores 1/10; otherwise at all other phases, the VAS score was 0. The average time for surgery was statistically longer in the WALANT group (61.22 minutes) compared to the GA group (55.33 minutes) (p = 0.003). There was no statistical difference in mean blood loss in both groups. The average post-operative VAS showed statistical significance only at 1 hour and 12 hours post-operation with no statistical difference at 2 and 24 hours post-operation. There was no difference in the post-operative ROM including wrist flexion, extension, supination and pronation for both groups up to six months' follow-up. CONCLUSION: There was no statistically significant difference in terms of preoperative anxiety level, intraoperative and post-operative VAS score, amount of blood loss and clinical outcome in both groups for plating of the distal end radius. However, the operating time was slightly longer in the WALANT group. We conclude that distal radius plating under WALANT has similar outcomes to GA. In centres with limited resources, WALANT offers a safe, reliable and cheaper option, reserving GA time for head, abdominal and thoracic surgery.

Post-operative Sore Throat: Comparing the Monitored Endotracheal Tube Cuff Pressure and Pilot Balloon Palpation Methods.

BACKGROUND: Endotracheal tube cuff (ETTc) inflation pressure is usually not regarded as an important aspect during intubation. In this study, we compared measuring ETTc pressure and pilot balloon palpation method in causing post-operative airway complications. METHODS: Two hundred and ninety-two surgical patients requiring intubation were recruited into this prospective, double-blind, randomised controlled study. Group A patients had their ETTc initially inflated, checked by a cuff pressure gauge, recorded and then set to 25 cmH2O. Group B patients had their ETTc inflated using the pilot balloon palpation method. Patients were then followed up for post-operative sore throat, hoarseness and cough. RESULTS: The overall incidence of post-operative sore throat was 39.0% versus 75.3% (P < 0.001), hoarseness 6.2% versus 15.1% (P < 0.05) and cough 7.5% versus 21.9% (P < 0.05) in Group A and B, respectively. Group A patients experienced a significant reduction in the incidence and severity of sore throat up to 24 h post-operatively (P < 0.001), hoarseness at the first hour (P = 0.004) and cough at first and 12 h post-operatively (P = 0.002). CONCLUSION: Adjusting the ETTc pressure to 25 cmH2O reduces post-operative sore throat, hoarseness and cough compared to pilot balloon palpation method.

Normal saline versus balanced-salt solution as intravenous fluid therapy during neurosurgery: effects on acid-base balance and electrolytes.

BACKGROUND: This prospective, randomized controlled study compared the changes in acid-base balance and serum electrolytes with the use of intravenous balanced and non-balanced crystalloid solutions intraoperatively during elective neurosurgery. METHODS: Thirty consented adult patients who underwent craniotomy were randomly allocated into two groups of 15 patients each. The non-balanced group received 0.9% normal saline while the balanced group received Sterofundin®ISO as the intraoperative fluid for maintenance. Biochemical indices for acid-base balance and serum electrolytes were analyzed periodically. RESULTS: In the non-balanced group, significant changes were noted in the pH, base excess and bicarbonate values over time compared to its respective baseline values (P<0.01). Four patients (27.7%) also developed a pH<7.35 and 5 patients (33.3%) developed marked acidosis with base excess <-4.0 at the end of surgery. Both mean sodium and chloride levels were also significantly higher compared to its baseline values respectively (142.6±2.4 versus 138±2.7 mmol/L, P<0.01 and 105.7±4.1 versus 113.2±3.0 mmol/L (P<0.01). CONCLUSIONS: A balanced solution (Sterofundin®ISO) provided significantly better control over acid-base balance, sodium and chloride levels when used as intraoperative fluid maintenance and replacement during elective neurosurgery.

Comparing insertion characteristics on nasogastric tube placement by using GlideScopeTM visualization vs. MacIntosh laryngoscope assistance in anaesthetized and intubated patients / Comparação das características de inserção de sonda nasogástrica, usando visibilização pelo laringoscópio GlideScope® vs. guiada pelo laringoscópio MacIntosh em pacientes anestesiados e intubados

Abstract Background and objective: This was a prospective, randomized clinical study to compare the success rate of nasogastric tube insertion by using GlideScopeTM visualization versus direct MacIntosh laryngoscope assistance in anesthetized and intubated patients. Methods: Ninety-six ASA I or II patients, aged 18-70 years were recruited and randomized into two groups using either technique. The time taken from insertion of the nasogastric tube from the nostril until the calculated length of tube had been inserted was recorded. The success rate of nasogastric tube insertion was evaluated in terms of successful insertion in the first attempt. Complications associated with the insertion techniques were recorded. Results: The results showed success rates of 74.5% in the GlideScopeTM Group as compared to 58.3% in the MacIntosh Group (p = 0.10). For the failed attempts, the nasogastric tube was successfully inserted in all cases using rescue techniques. The duration taken in the first attempt for both techniques was not statistically significant; Group A was 17.2 ± 9.3 s as compared to Group B, with a duration of 18.9 ± 13.0 s (p = 0.57). A total of 33 patients developed complications during insertion of the nasogastric tube, 39.4% in Group A and 60.6% in Group B (p = 0.15). The most common complications, which occurred, were coiling, followed by bleeding and kinking. Conclusion: This study showed that using the GlideScopeTM to facilitate nasogastric tube insertion was comparable to the use of the MacIntosh laryngoscope in terms of successful rate of insertion and complications.

Resumo Justificativa e objetivo: Este foi um estudo clínico prospectivo e randômico para comparar a taxa de sucesso da inserção de sonda nasogástrica (NG) com as técnicas de visibilização guiada pelo laringoscópio GlideScope® versus guiada pelo laringoscópio MacIntosh em pacientes anestesiados e intubados. Métodos: Foram recrutados 96, ASA I ou II, entre 18-70 anos, e divididos randomicamente em dois grupos, com uma ou outra técnica. Foi calculado o tempo transcorrido desde a inserção da sonda NG, da narina até a inserção do comprimento calculado da sonda. A taxa de sucesso de inserção da sonda NG foi avaliada quanto à inserção bem-sucedida na primeira tentativa. As complicações associadas às técnicas de inserção foram registradas. Resultados: Os resultados mostraram taxas de sucesso de 74,5% para o grupo GlideScope® em comparação com 58,3% para o grupo MacIntosh (p = 0,10). Para as tentativas que falharam, a sonda NG foi inserida com sucesso em todos os casos, com as técnicas de resgate. A duração da primeira tentativa para ambas as técnicas não foi estatisticamente significativa: 17,2 ± 9,3 segundos no Grupo A e 18,9 ± 13,0 segundos no Grupo B (p = 0,57). No total, 33 pacientes desenvolveram complicações durante a inserção da sonda NG: 39,4% no Grupo A e 60,6% no Grupo B (p = 0,15). As complicações mais comuns ocorridas foram enrolamento, seguido de sangramento e dobradura. Conclusão: Este estudo mostrou que o uso do GlideScope® para facilitar a inserção de sonda nasogástrica foi comparável ao uso do laringoscópio MacIntosh quanto à taxa de sucesso de inserção e às complicações.

Comparing insertion characteristics on nasogastric tube placement by using GlideScope™ visualization vs. MacIntosh laryngoscope assistance in anaesthetized and intubated patients.

BACKGROUND AND OBJECTIVE: This was a prospective, randomized clinical study to compare the success rate of nasogastric tube insertion by using GlideScope™ visualization versus direct MacIntosh laryngoscope assistance in anesthetized and intubated patients. METHODS: Ninety-six ASA I or II patients, aged 18-70 years were recruited and randomized into two groups using either technique. The time taken from insertion of the nasogastric tube from the nostril until the calculated length of tube had been inserted was recorded. The success rate of nasogastric tube insertion was evaluated in terms of successful insertion in the first attempt. Complications associated with the insertion techniques were recorded. RESULTS: The results showed success rates of 74.5% in the GlideScope™ Group as compared to 58.3% in the MacIntosh Group (p=0.10). For the failed attempts, the nasogastric tube was successfully inserted in all cases using rescue techniques. The duration taken in the first attempt for both techniques was not statistically significant; Group A was 17.2±9.3s as compared to Group B, with a duration of 18.9±13.0s (p=0.57). A total of 33 patients developed complications during insertion of the nasogastric tube, 39.4% in Group A and 60.6% in Group B (p=0.15). The most common complications, which occurred, were coiling, followed by bleeding and kinking. CONCLUSION: This study showed that using the GlideScope™ to facilitate nasogastric tube insertion was comparable to the use of the MacIntosh laryngoscope in terms of successful rate of insertion and complications.

[Comparing insertion characteristics on nasogastric tube placement by using GlideScope™ visualization vs. MacIntosh laryngoscope assistance in anaesthetized and intubated patients]. / Comparação das características de inserção de sonda nasogástrica, usando visibilização pelo laringoscópio GlideScope(®) vs. guiada pelo laringoscópio MacIntosh em pacientes anestesiados e intubados.

BACKGROUND AND OBJECTIVE: This was a prospective, randomized clinical study to compare the success rate of nasogastric tube insertion by using GlideScope™ visualization versus direct MacIntosh laryngoscope assistance in anesthetized and intubated patients. METHODS: Ninety-six ASA I or II patients, aged 18-70 years were recruited and randomized into two groups using either technique. The time taken from insertion of the nasogastric tube from the nostril until the calculated length of tube had been inserted was recorded. The success rate of nasogastric tube insertion was evaluated in terms of successful insertion in the first attempt. Complications associated with the insertion techniques were recorded. RESULTS: The results showed success rates of 74.5% in the GlideScope™ Group as compared to 58.3% in the MacIntosh Group (p=0.10). For the failed attempts, the nasogastric tube was successfully inserted in all cases using rescue techniques. The duration taken in the first attempt for both techniques was not statistically significant; Group A was 17.2±9.3s as compared to Group B, with a duration of 18.9±13.0s (p=0.57). A total of 33 patients developed complications during insertion of the nasogastric tube, 39.4% in Group A and 60.6% in Group B (p=0.15). The most common complications, which occurred, were coiling, followed by bleeding and kinking. CONCLUSION: This study showed that using the GlideScope™ to facilitate nasogastric tube insertion was comparable to the use of the MacIntosh laryngoscope in terms of successful rate of insertion and complications.

Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer.

Expression of matrix metalloproteinase 9 (MMP9) is elevated in a variety of inflammatory and oncology indications, including ulcerative colitis and colorectal cancer. MMP9 is a downstream effector and an upstream mediator of pathways involved in growth and inflammation, and has long been viewed as a promising therapeutic target. However, previous efforts to target matrix metalloproteinases (MMPs), including MMP9, have utilized broad-spectrum or semi-selective inhibitors. While some of these drugs showed signs of efficacy in patients, all MMP-targeted inhibitors have been hampered by dose-limiting toxicity or insufficient clinical benefit, likely due to their lack of specificity. Here, we show that selective inhibition of MMP9 did not induce musculoskeletal syndrome (a characteristic toxicity of pan-MMP inhibitors) in a rat model, but did reduce disease severity in a dextran sodium sulfate-induced mouse model of ulcerative colitis. We also found that MMP9 inhibition decreased tumor growth and metastases incidence in a surgical orthotopic xenograft model of colorectal carcinoma, and that inhibition of either tumor- or stroma-derived MMP9 was sufficient to reduce primary tumor growth. Collectively, these data suggest that selective MMP9 inhibition is a promising therapeutic strategy for treatment of inflammatory and oncology indications in which MMP9 is upregulated and is associated with disease pathology, such as ulcerative colitis and colorectal cancer. In addition, we report the development of a potent and highly selective allosteric MMP9 inhibitor, the humanized monoclonal antibody GS-5745, which can be used to evaluate the therapeutic potential of MMP9 inhibition in patients.

Profile etching for prefiguring X-ray mirrors.

A method to pre-shape mirror substrates through etching with a broad-beam ion source and a contoured mask is presented. A 100 mm-long elliptical cylinder substrate was obtained from a super-polished flat Si substrate with a 48 nm root-mean-square (r.m.s.) figure error and a 1.5 Šr.m.s. roughness after one profile-etching process at a beam voltage of 600 V without iteration. A follow-up profile coating can be used to achieve a final mirror. Profile etching and profile coating combined provide an economic way to make X-ray optics, such as nested Kirkpatrick-Baez mirrors.

High-throughput kinetic screening of hybridomas to identify high-affinity antibodies using bio-layer interferometry.

Kinetic analysis of antibodies is crucial in both clone selection and characterization. Historically, antibodies in supernatants from hybridomas are selected based on a solid-phase enzyme-linked immunosorbent assay (ELISA) in which the antigen is immobilized on the assay plate. ELISA selects clones based on a combination of antibody concentration in the supernatant and affinity. The antibody concentration in the supernatant can vary significantly and is typically unknown. Using the ELISA method, clones that express high levels of a low-affinity antibody can give an equivalent signal as clones that express low levels of a high-affinity antibody. As a consequence, using the ELISA method, superior clones can be overshadowed by inferior clones. In this study, we have applied Bio-Layer Interferometry to screen hybridoma clones based on disassociation rates using the OctetRED 384 platform. Using the OctetRED platform, we were able to screen 2000 clones within 24 hours and select clones containing high-affinity antibodies for further expansion and subsequent characterization. Using this method, we were able to identify several clones producing high-affinity antibodies that were missed by ELISA.

Reduction of the dimensionality of the EEG channels during scoliosis correction surgeries using a wavelet decomposition technique.

This paper presents a comparison between the electroencephalogram (EEG) channels during scoliosis correction surgeries. Surgeons use many hand tools and electronic devices that directly affect the EEG channels. These noises do not affect the EEG channels uniformly. This research provides a complete system to find the least affected channel by the noise. The presented system consists of five stages: filtering, wavelet decomposing (Level 4), processing the signal bands using four different criteria (mean, energy, entropy and standard deviation), finding the useful channel according to the criteria's value and, finally, generating a combinational signal from Channels 1 and 2. Experimentally, two channels of EEG data were recorded from six patients who underwent scoliosis correction surgeries in the Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM) (the Medical center of National University of Malaysia). The combinational signal was tested by power spectral density, cross-correlation function and wavelet coherence. The experimental results show that the system-outputted EEG signals are neatly switched without any substantial changes in the consistency of EEG components. This paper provides an efficient procedure for analyzing EEG signals in order to avoid averaging the channels that lead to redistribution of the noise on both channels, reducing the dimensionality of the EEG features and preparing the best EEG stream for the classification and monitoring stage.

Subnanoradian X-ray phase-contrast imaging using a far-field interferometer of nanometric phase gratings.

Hard X-ray phase-contrast imaging characterizes the electron density distribution in an object without the need for radiation absorption. The power of phase contrast to resolve subtle changes, such as those in soft tissue structures, lies in its ability to detect minute refractive bending of X-rays. Here we report a far-field, two-arm interferometer based on the new nanometric phase gratings, which can detect X-ray refraction with subnanoradian sensitivity, and at the same time overcomes the fundamental limitation of ultra-narrow bandwidths (Δλ/λ~10⁻4) of the current, most sensitive methods based on crystal interferometers. On a 1.5% bandwidth synchrotron source, we demonstrate clear visualization of blood vessels in unstained mouse organs in simple projection views, with over an order-of-magnitude higher phase contrast than current near-field grating interferometers.