Soft Spot Research Articles

Pre- and Post-Improvement Performance of a Railway Embankment Stabilized with Ductile Inclusions

Large deflections and accumulation of permanent track geometry defects at railway soft spots cause significant operational issues including increased maintenance costs, decreased train speed, and, at an extreme, derailments and track failures. Reinforcing inclusions placed between the ties are a promising rehabilitation scheme to locally stabilize the embankment and transfer the loads to deeper, more suitable soils. In this paper we report the results of a long-term monitoring program to assess the performance of ductile inclusions, known commercially as “GeoSpike® elements”, to stabilize a rapidly deteriorating railway soft spot. Observations of track bed behavior are presented for 8 months prior to installation and 15 months after installation using a combination of LIDAR, Digital Image Correlation (DIC), and ShapeAccelArrays (SAA). Through the monitoring program, it was determined that the ductile inclusions decreased the average rate of deterioration by a factor of approximately 3, which allowed the frequency of site maintenance to be decreased from three times a year to once a year.

Autologous minced cartilage implantation for focal cartilage lesions of the humeral capitellum

The goal of minced cartilage implantation (MCI) is to restore an intact cartilage surface in focal osteochondral lesions of the humeral capitellum. The indications for MCI are limited osteochondral lesions at the humeral capitellum, also at the head of the radius, with intact cartilage border as well as in situ or acompletely detached fragment, and free joint bodies (gradeII-gradeV according to Hefti). Contraindications for MCI are already concomitant or associated cartilage damage as well as bilateral osteochondral lesions and insufficient available cartilage material. After diagnostic arthroscopy to detect possible concomitant pathologies and to exclude already corresponding cartilage lesions, the arthroscope is flipped posterolaterally over the high posterolateral portal and asecond portal is created under visualization via the soft spot. Initially, debridement of the focal cartilage defect, assessment of the marginal zone, and/or salvage of free joint bodies. Using asmooth shaver and the filter provided, the partially or even completely detached cartilage fragment is unidirectionally fragmented under continuous suction. The remaining defect with astable marginal zone is cleanly curetted, and the joint is completely dried. The fragmented cartilage collected in the filter is bonded to amembrane using autologous conditioned plasma (ACP) and then arthroscopically applied to the defect via acannula, sealed using thrombin and fibrin. Postoperative immobilization in acast for at least 24 h is required. Afterwards, free exercise of the joint is possible, but no loading should be maintained for 6weeks. Return to sport after 3months. Good to very good clinical and MRI morphologic results are already evident in the short-term course. Prospective and retrospective multicenter studies are needed to evaluate future long-term results.

Leveraging High-Resolution Ion Mobility-Mass Spectrometry for Cyclic Peptide Soft Spot Identification.

Cyclic peptides are an important class of molecules that gained significant attention in the field of drug discovery due to their unique pharmacological characteristics and enhanced proteolytic stability. Yet, gastrointestinal degradation remains a major hurdle in the discovery of orally bioavailable cyclic peptides. Soft spot identification (SSID) of the regions in the cyclic peptide sequence susceptible to amide hydrolysis by proteases is used in the discovery stage to guide medicinal chemistry design. SSID can be an arduous task, traditionally performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), often resulting in complex and time-consuming manual analysis, particularly when isomeric linear peptide metabolites chromatographically coelute. Here, we present an alternative orthogonal approach that entails a high-resolution ion mobility (HRIM) system based on Structures for Lossless Ion Manipulation (SLIM) technology interfaced with quadrupole time-of-flight (QTOF) mass spectrometry to address some of the challenges associated with SSID. Two strategies were used to resolve linear isomeric peptide metabolites: labeled and label-free, both utilizing the HRIM platform. The label-free strategy leverages negative polarity to ionize the isomers which achieves better separation of the gas phase ions in the ion mobility (IM) dimension as compared to positive polarity, which is a more conventional approach when studying proteins and peptides. The second approach uses an isotope-labeled dimethyl tag on the terminal amine group, acting as a "shift reagent" to influence the mobility of isomers in the positive mode. This method resulted in baseline separation for the isomers of interest and produced unique product ions in the fragmentation spectra for unambiguous soft spot identification. Both label-free and labeled strategies demonstrated the ability to solve the challenges associated with SSID for cyclic peptides.

The Unwanted Soft Spot: A Rare Case of Biventricular Non-compaction Cardiomyopathy Causing Heart Failure in an Adult Filipino Male

Biventricular non-compaction cardiomyopathy is a rare genetic cardiomyopathy caused by an early cessation of compaction of trabecular meshwork during embryogenesis. The clinical manifestations range from asymptomatic to severe reduced ventricular dysfunction. We present a rare case of biventricular non-compaction cardiomyopathy in an adult Filipino male presenting with heart failure symptoms. A 61-year-old male presented with a 1-year history of easy fatigability accompanied by bipedal oedema. ECG showed AF in rapid ventricular response. Echocardiography revealed wall motion abnormality with mid-range ejection fraction. Cardiac MRI showed biventricular dilatation with reduced systolic function. He was stable throughout the hospital stay and discharged with guideline-directed heart failure medications. Biventricular non-compaction cardiomyopathy is rare. However, it can be seen as a spectrum of phenotypic manifestations as this may be a form of cardiomyopathies. The management primarily depends on the clinical manifestation, as no specific treatment protocol exists. A correct diagnosis is essential because of the possible associations and the need for long-term management and screening of family members.

Rapid and Definitive Identification of Cyclic Peptide Soft Spots by Isotope-Labeled Reductive Dimethylation and Mass Spectrometry Fragmentation.

Cyclic peptides are an emerging therapeutic modality over the past few decades. To identify drug candidates with sufficient proteolytic stability for oral administration, it is critical to pinpoint the amide bond hydrolysis sites, or soft spots, to better understand their metabolism and provide guidance on further structure optimization. However, the unambiguous characterization of cyclic peptide soft spots remains a significant challenge during early stage discovery studies, as amide bond hydrolysis forms a linearized isobaric sequence with the addition of a water molecule, regardless of the amide hydrolysis location. In this study, an innovative strategy was developed to enable the rapid and definitive identification of cyclic peptide soft spots by isotope-labeled reductive dimethylation and mass spectrometry fragmentation. The dimethylated immonium ion with enhanced MS signal at a distinctive m/z in MS/MS fragmentation spectra reveals the N-terminal amino acid on a linearized peptide sequence definitively and, thus, significantly simplifies the soft spot identification workflow. This approach has been evaluated to demonstrate the potential of isotope-labeled dimethylation to be a powerful analytical tool in cyclic peptide drug discovery and development.

Green synthesis of silver nanoparticles by sweet cherry and its application against cherry spot disease

Asia has a rich history of cultivating sweet cherries, a practice that has been carried out since ancient times. However, the effective management of Alternaria disease in sweet cherry crops has presented a formidable challenge, resulting in notable decreases in yield. Various attempts have been made to employ both chemical and biological treatments; however, their effectiveness has been restricted. In order to tackle this problem, an investigation was carried out, with the primary objective of isolating and identifying Alternaria isolates that are accountable for the occurrence of sweet cherry soft spot rot. Out of the twelve isolates examined, the CHM-4 isolate was found to be the most pathogenic. Its identification was achieved through the use of the ITS genomic region (ITS1 and ITS4), and the BLAST results revealed a 95 % similarity with Alternaria alternata (MG744381.1). The objective of the research was to explore the potential of silver nanoparticles (SNPs) synthesized by phytosynthesis as a novel antifungal agent to combat sweet cherry soft spot pathogenicity. The biosynthesis of SNPs was carried out using sweet cherry fruits kernel exudate, which served as an environmentally friendly source. The exudates exhibited the ability to produce nanoparticles with an average size of 24.97 nm. Analysis conducted using a transmission electron microscope (TEM) revealed the multifaceted structure of these nanoparticles. Furthermore, when tested at concentrations of 5, 10, 20, and 40 μg/ml, these biosynthetic nanoparticles demonstrated the capability to inhibit the growth of Alternaria fungi and effectively destroy fungal hyphae. It is advisable to utilize diverse components of sweet cherry for the synthesis of various nanoparticles owing to their compatibility with the surrounding environment.

An anatomic consideration of the femoral nerve during direct anterior hip approach: A cadaveric study.

This study aimed to investigate the distance and correlation between the anatomy of the anterior side of the hip joint and the femoral nerve. Using ten fresh-frozen cadavers with twenty hip joints. We dissected and marked the femoral nerve in the inguinal area. Employing the direct anterior approach, we identified and marked study points, including the superior and inferior points of the anterior rim of the acetabulum, ¼ point, half point, and ¾ point along an imagined line connecting the formers, the inferomedial and mid aspect of the femoral neck, and the soft spot. Coronal plane measurements gauged the distance between these points and the femoral nerve. The collected data were analyzed to assess the distance and correlation. In the coronal plane, the median distance between the inferior point of the anterior rim of the acetabulum and the femoral nerve was 0 millimeters (interquartile range [IQR] 0-0). Likewise, the median distance between the mid aspect of the medial side of the femoral neck and the femoral nerve was 0 millimeters (IQR 0-0). Additionally, the mean distance between the soft spot and the femoral nerve was 1.18cm (SD 0.63). Surgeons approaching the hip joint via the direct anterior approach should be cautious at the inferior point of the anterior rim of the acetabulum and the mid aspect of the femoral neck. The soft spot at the anterior rim of the acetabulum remains safe from direct injury when surgeons use the correct technique during anterior retractor insertion.

A study to assess the effectiveness of planned teaching regarding the harmful effect of oil application on anterior fontanels of newborn among post-natal mothers

The anterior fontanelle, sometimes known as the “soft spot,” is an important anatomical component in neonates that allows brain growth and development. Possible harm is caused by such practices, as they may result in unfavorable outcomes, such as skin irritation and a delay in fontanelle closure. The goal of this study was to see how effective pre-planned education was at informing postpartum women about the dangers of applying oil to newborns’ anterior fontanelles. The study was conducted with the goal of increasing the understanding of the adverse effects of oil application on the anterior fontanels of newborns among postnatal mothers, The study will be thoroughly described to the participants, and their written Consent will be taken for the participate in the study and publishing the information. Sampling technique will be convenient. Population and sampling techniques will be examined. Mothers will be the target group with a sample size of 60 postnatal mothers. The sample will be drawn using The Purposive sampling approach. Prior authorization will be acquired from the designated hospitals’ higher authority. The inclusion criteria will be used to select samples. Information will be gathered from the hospital’s obstetric ward. First, pretest knowledge of the adverse effects of applying oil to newborns’ anterior fontanels among postnatal mothers was assessed. Postnatal mothers will be taught about the detrimental effects of placing oil on the anterior fontanels of their newborns. The post-test assessment of knowledge regarding the adverse effects of applying oil to anterior fontanels was performed after 7 days. If the hypothesis of our study is helpful in improving mothers’ knowledge in the post-test rather than pre-test following the intended training.

Neo-Ottoman Turk-Scape: Analyzing the Role of Dizis as Türkiye’s Soft Power

Türkiye has grabbed the world’s attention in the last three decades for its strategic use of soft power as an instrument of cultural diplomacy. Buoyed by relative economic success in the post-Cold War period, the new ruling elites of Türkiye used Islamic practices and value-system, particularly its Ottoman past, as tools of the soft power in cultural diplomacy. Turkish dizis (television series), particularly those based on historical figures, have played a critical role in the nation branding exercise of Türkiye. These dizis have not only created a soft spot for the country, and boosted its tourism, but it also helped the government, particularly President Recep Tayyip Erdoğan project himself as a leader with potentials to lead the Muslim world or Ummah. This article assesses the role of Turkish dizis as a soft power instrument in cultural diplomacy and the nation branding of Türkiye. Interestingly, Turkish dizis were primarily produced for domestic consumption, and were not necessarily targeting foreign audience, at least in the beginning. Thus, they perform the dual function of molding public opinion within the country, while also helping create a positive image about Türkiye and its past among the foreign audience. But nostalgia of the past alone is not sufficient, if not complemented by reciprocal actions on the ground.

To Paint a New Picture: Into the Lives of Eldest Siblings of Separated Fami-lies during COVID-19

This study emerged to enable humanitarian organizations to provide better services for children in separated families by understanding eldest siblings' lived experiences. Through Husserlian’s descriptive phenomenology utilizing Colaizzi’s method of data analysis, six participants were interviewed online at the height of the pandemic in 2021-2022 in Cebu City, Philippines. Data were transcribed using data reduction methods and revealed 6 themes: (1) "Having to always be the bigger person": Role Intensification; (2)"Devoting myself to things that weren't supposed to land on me": Adult Difficulties; (3) "Becoming stronger and keeping a soft spot"; Growing in Stature; (4) "True brothers are there for you”: The Support Given to the Supporter; (5) “To be free but mindful:'' Motivation to Persevere; (6) “To paint a better picture of life: ''Setting and Living an Example. The researchers discovered that the eldest siblings were forced to take charge of responsibilities that were not supposed to be theirs; encountered emotional difficulties such as loneliness and anxiety in facing a wide range of familial, developmental, and logistical problems; coped through these challenges with social support, religious devotion, and modern entertainment; and devoted their lives to protecting their siblings and giving them the lives they deserve. From these results, the researchers recommend that counseling is provided for the eldest siblings to enable the development of support structures and meaningful relationships that propel the eldest siblings to persevere.

There Is a Lot More to Transplantation Surgery Than the Surgery Itself: The "Other" Sir Peter John Morris, AC, FRS.

There Is a Lot More to Transplantation Surgery Than the Surgery Itself: The "Other" Sir Peter John Morris, AC, FRS.

Discovery of Ghrelin(1-8) Analogues with Improved Stability and Functional Activity for PET Imaging.

The highest affinity ghrelin-based analogue for fluorine-18 positron emission tomography, [Inp1,Dpr3(6-FN),1Nal4,Thr8]ghrelin(1-8) amide (1), has remarkable subnanomolar receptor affinity (IC50 = 0.11 nM) toward the growth hormone secretagogue receptor 1a (GHSR). However, initial in vivo PET imaging and biodistribution of [18F]1 in mice demonstrated an unfavorable pharmacokinetic profile with rapid clearance and accumulation in liver and intestinal tissue, prompting concerns about the metabolic stability of this probe. The aims of the present study were to examine the proteolytic stability of ghrelin analogue 1 in the presence of blood and liver enzymes, structurally modify the peptide to improve stability without impeding the strong binding affinity, and measure the presently unknown functional activity of ghrelin(1-8) analogues. The in vitro stability and metabolite formation of 1 in human serum and liver S9 fraction revealed a metabolic soft spot between amino acids Leu5 and Ser6 in the peptide sequence. A focused library of ghrelin(1-8) analogues was synthesized and evaluated in a structure-activity-stability relationship study to further understand the structural importance of the residues at these positions in the context of stability and receptor affinity. The critical nature of l-stereochemistry at position 5 was identified and substitution of Ser6 with l-2,3-diaminopropionic acid led to a novel ligand with substantially improved in vitro stability while maintaining subnanomolar GHSR affinity. Despite the highly modified nature of these analogues compared to human ghrelin, ghrelin(1-8) analogues were found to recruit all G protein subtypes (Gαq/11/13/i1/oB) known to associate with GHSR as well as β-arrestins with low micromolar to nanomolar potencies. The study of these analogues demonstrates the ability to balance desirable ligand properties, including affinity, stability, and potency to produce well-rounded candidate molecules for further in vivo evaluation.

Computed Tomography Provides Effective Detection of Traumatic Arthrotomy of the Elbow.

Failure to identify a traumatic arthrotomy of the elbow (TAE) can lead to septic arthritis with devastating complications. The gold standard for TAE detection remains controversial, and evidence is limited. While multiple clinical and cadaveric studies have validated the use of computed tomography (CT) to detect traumatic arthrotomies about the knee, other studies have called into question whether the use of CT to detect traumatic arthrotomy is applicable to the elbow. A prior cadaveric study utilizing a direct posterior (transtendon) traumatic arthrotomy model failed to detect traumatic arthrotomy via CT in 100% of cases11. The aim of this study was to determine the sensitivity and specificity for detecting TAE with CT, utilizing a lateral traumatic arthrotomy model. Ten fresh-frozen upper extremity transhumeral cadaveric specimens were utilized. Only specimens with an intact elbow joint and no known elbow surgery or injury were included. CT scans were performed to screen for intra-articular air prior to arthrotomy. A full thickness 10 mm incision was performed over the soft spot, just distal to the lateral epicondyle. The elbow was taken through full range of motion in flexion and extension, as well as forearm pronation and supination 10 times. CT scans were then repeated and screened for the presence of intra-articular air. Lastly, a saline load test was performed on all specimens, and the volume of saline required to detect the arthrotomy was recorded. Of the 10 specimens, 0% (n=0) demonstrated intra-articular air of the elbow joint on CT scan prior to arthrotomy, and 100% (n=10) demonstrated intra-articular air on CT scan following arthrotomy. CT scan demonstrated 100% sensitivity and 100% specificity for TAE. For the saline load test, 90% (n=9) were positive for TAE at an average of 12 mL (range: 4mL-47mL), providing 90% sensitivity. In this cadaveric study utilizing a more commonly observed direct lateral traumatic laceration, CT was able to detect 100% (n=10) of TAEs with 100% sensitivity and specificity. These results show that CT scans can effectively diagnose lateral traumatic arthrotomy in a cadaveric model and can be a viable option for diagnosis in a clinical setting. Clinical correlation is required to confirm in these in vitro findings.

Can elbow arthroscopic posterior portals damage the anconeus nerve? A cadaveric study.

Neurological injuries are among the most reported complications of elbow arthroscopy. Several cadaveric studies have assessed the relationship between nerves and arthroscopic portals. To our knowledge, no studies evaluated the anconeus nerve. This anatomic study aimed to identify the course of the anconeus nerve and to investigate its anatomic relation with posterior elbow portals, providing useful information to preserve it during surgery. Twelve fresh frozen elbows were dissected to isolate the radial nerve and its branch to the anconeus muscle. Distances between the anconeus nerve, olecranon tip, and lateral epicondyle were measured. Posterior, posterolateral and soft spot portals were created and their proximity to the nerve was measured. The anconeus nerve showed an average distance from the lateral epicondyle of 19.67 mm (SD 1.44 mm) and from the olecranon of 22.33 mm (SD 1.72 mm). The posterolateral portal was 1 mm medial to the nerve. The soft spot portal was located where the nerve enters the muscle. An important finding of this study was the closeness between the anconeus nerve and the posterolateral and soft spot portals, resulting in a high risk of nerve damage. More medial placement of the posterolateral portal may avoid anconeus nerve injury and consequent muscle denervation.

YOGA OF A YOGINI: IN CONTEXT TO FEMINIE ENERGY

Introduction: Since antiquity the contest of strength between Shaivism and Bhaktism has been in fashion. If the propounder of Shaivism owe their allegiance to Lord Shiva, the adherents of Bhaktism have a soft spot for Lord Vishnu. The former is hailed as the God of Destroyer (of maya), the latter of the universal householder or the Preserver. The emblematic indications of these two sects are vividly pronounced and detailed. The former smears tilak(a distinctive spot of coloured powder or paste smeared on the forehead by both gender as an emblem to the allegiance that they owe to) called as Tripundra is three liners(indications of the triguna:satvika,tamasika and rajasika) on their forehead horizontally; while the latter smears Vishnu-Tilak called as Urdhvapundra or upward-U shaped feet of Lord Vishnu that the devotees smear on their forehead, indicating that the devo- tee looks upward for possible upliftment from material world to spiritual world and finally, to liberation or moksha. Interestingly, if ’Hari’ is the other name of Lord Vishnu that the devotees utter;’HaraHara Mahadev’(That Mahadeva or the God of Devtas reside in everyone, har)is the slogan that the devotees of Shiva scream out.1 [Mubeen and ShahMubeen and Shah]

Generaal JH De la Rey in Mei 1902: 'n Bittereinder vir vrede

General J.H. de la Rey in May 1902: a die-hard Boer opting for peace General J.H. (Koos) de la Rey was, according to historians, a Christian Afrikaner and a Boer aristocrat. Not only did he play a leading role in the Boer community of the old Transvaal – in the 1890s he was a well-known member of the Volksraad or highest governing authority in the South African Republic – but in the Anglo-Boer War of 1899–1902 he became a Boer general who distinguished himself by leading his burgers in attacks on British military structures and skirmishes on horseback. De la Rey became known as a military strategist of the first rank. In the run-up to the Anglo-Boer War, which started on 11 October 1899, De la Rey tried to avoid this war with Britain as long as he could. After the war became a reality, he gave himself for his country as a die-hard fighter or “bittereinder”: somebody who fights till the bitter end. Apart from his natural military abilities, General De la Rey had a soft spot and a feeling for stressed people. He helped badly wounded enemies and in May 1902, in Boer talks about peace, he listened with compassion to those Boers who had suffered much and pleaded for peace, convincing him that they had reached the end of their tether – literally the end of the bitter end. De la Rey did not speak much at meetings, but during the peace talks at Vereeniging from 15–31 May 1902, he urged and influenced his people to accept Britain’s peace proposals. In the end, De la Rey and the die-hard fighters among the Boers who had fought for their political independence against British imperialism fought for self-rule under British rule as soon as possible. De la Rey wanted the Afrikaner people to maintain their identity as a nation in new circumstances and not to be wiped out as a nation through the Anglo-Boer War. He died as a leader and a hero of his people in 1914.

Generaal JH De la Rey in Mei 1902: 'n Bittereinder vir Vrede

Abstract: General J.H. de la Rey in May 1902: a die-hard Boer opting for peace General J.H. (Koos) de la Rey was, according to historians, a Christian Afrikaner and a Boer aristocrat. Not only did he play a leading role in the Boer community of the old Transvaal – in the 1890s he was a well-known member of the Volksraad or highest governing authority in the South African Republic – but in the Anglo-Boer War of 1899–1902 he became a Boer general who distinguished himself by leading his burgers in attacks on British military structures and skirmishes on horseback. De la Rey became known as a military strategist of the first rank. In the run-up to the Anglo-Boer War, which started on 11 October 1899, De la Rey tried to avoid this war with Britain as long as he could. After the war became a reality, he gave himself for his country as a die-hard fighter or “bittereinder”: somebody who fights till the bitter end. Apart from his natural military abilities, General De la Rey had a soft spot and a feeling for stressed people. He helped badly wounded enemies and in May 1902, in Boer talks about peace, he listened with compassion to those Boers who had suffered much and pleaded for peace, convincing him that they had reached the end of their tether – literally the end of the bitter end. De la Rey did not speak much at meetings, but during the peace talks at Vereeniging from 15–31 May 1902, he urged and influenced his people to accept Britain’s peace proposals. In the end, De la Rey and the die-hard fighters among the Boers who had fought for their political independence against British imperialism received fought for self-rule under British rule as soon as possible. De la Rey wanted the Afrikaner people to maintain their identity as a nation in new circumstances and not to be wiped out as a nation through the Anglo-Boer War. He died as a leader and a hero of his people in 1914.

Trevor J. Dadson (1947–2020)

Trevor J. Dadson (1947–2020)

Soft Spot in Babies - Normal

Author: Barton Schmitt MD, FAAPDisclaimer: This health information is for educational purposes only. You the reader assume full responsibility for how you choose to use it. The information contained in this handout should not be used as a substitute for the medical care and advice of your pediatrician. Listing of any resources does not imply an endorsement.

2-Pyridine Carboxaldehyde for Semi-Automated Soft Spot Identification in Cyclic Peptides

Cyclic peptides are an attractive option as therapeutics due to their ability to disrupt crucial protein–protein interactions and their flexibility in display type screening strategies, but they come with their own bioanalytical challenges in metabolite identification. Initial amide hydrolysis of a cyclic peptide results in a ring opening event in which the sequence is linearized. Unfortunately, the mass of the singly hydrolyzed sequence is the same (M + 18.0106 Da) irrespective of the initial site of hydrolysis, or soft spot. Soft spot identification at this point typically requires time-consuming manual interpretation of the tandem mass spectra, resulting in a substantial bottleneck in the hit to lead process. To overcome this, derivatization using 2-pyridine carboxaldehyde, which shows high selectivity for the alpha amine on the N-terminus, was employed. This strategy results in moderate- to high-efficiency derivatization with a unique mass tag and diagnostic ions that serve to highlight the first amino acid in the newly linearized peptide. The derivatization method and analytical strategy are demonstrated on a whole cell lysate digest, and the soft spot identification strategy is shown with two commercially available cyclic peptides: JB1 and somatostatin. Effective utilization of the automated sample preparation and interpretation of the resulting spectra shown here will serve to reduce the hit-to-lead time for generating promising proteolytically stable peptide candidates.